<p>Chapter 1: The Study of Body Function  ______: study of how body works to maintain life  Pathophysiology: how physiological processes are altered in disease or injury Scientific Method  Form a testable hypothesis about observations  2. Conduct and analyze experiments to test hypothesis  3. Draw conclusions about whether or not results support hypothesis  4. Develop a ______ general statement explaining natural phenomena that is based on proven hypotheses Testing Hypothesis  Involves:  Experimental and ______groups  Quantitative measurements performed blindly  Analysis of data using statistics Developing new drugs  When a new drug is suggested by experiments:  Its effectiveness and toxicity is tested first in tissue culture, rats, mice  If effective and safe, clinical trials performed  Phase I Trials: Toxicity and metabolism tested in healthy human volunteers  Phase II Trials: Effectiveness and toxicity tested in target population  Phase III Trials: Widespread test of drug in diverse population  Phase IV Trials: Drug is tested for other potential uses Homeostasis  Is maintenance of a state of ______ In which conditions are stabilized above and below a physiological set point  By negative feedback loops  Sensor: Detects deviation from ______ Integrating center: Determines response  Effector: Produces response Regulatory mechanisms:  Intrinsic control is built into organ being regulated  ______control comes from outside of organ  E.g. body temperature is controlled by antagonistic effects of sweating and shivering  E.g. hormones control blood glucose levels</p><p>Positive feedback is rare because it amplifies changes  In producing blood clots  In females, LH surge that causes ovulation  In uterus and oxytocin during labor Negative feedback loops control blood pressure</p><p>Tissues: Muscles specialized for contraction Skeletal Is striated; ______ Each fiber forms by fusion of embryonic myoblasts  Allowing it to become large and ______ Is individually controlled  Lines up in parallel with other fibers to form bundles Cardiac Myocardial celIs:  Are short, striated and involuntary  Are branched to form a continuous fabric  Have ______between cells that provide mechanical and electrical interconnections  Are not individually controlled Smooth Is not striated; is involuntary  Found in many organs, tissues  Controlled by ANS Nervous Tissue  Consists of neurons and supporting or ______ Neurons are specialized for conducting electrical signals  Have a cell body, dendrites and axon  Cell body contains nucleus; is ______center  Dendrites: highly branched extensions off cell body  Receive inputs from other neurons  Axon: single, long extension off cell body  Conducts nerve impulses to other cells  Supporting/Glial cells provide physical and functional support for neurons  5X more abundant than neurons Epithelial  Lines and covers body surfaces  Consists of cells that form membranes and glands  Regularly replaced  Squamous epithelial cells are flattened  Columnar epithelial cells are taller than wide  ______epithelial cells are cube-shaped  Simple membranes are one cell thick  Specialized for transport  Stratified has a number of layers  Specialized for protection  Non-keratinized stratified squamous consists of living cells  Keratinized stratified squamous has outer layer of dead cells  Cells contain water-resistant ______ Cells joined by junctional complexes, which increase strength and create barrier  Separated from underlying tissue by basement membrane Exocrine Glands  Derived from epithelial cells  Secrete onto epithelium via ducts  Can be simple tubes or clusters called acini  Whose secretion is controlled by surrounding myoepithelial cells Connective Tissue  Lots of extracellular material in space between its cells  Eg:connective tissue proper, cartilage, bone and blood  Loose connective tissue consists of ______(fibrous proteins) and tissue fluid  E.g. dermis of skin  Dense fibrous connective tissue has fibers of collagen  regularly arranged as in tendons  Or irregularly oriented as in capsules, sheaths Adipose  Specialized for fat synthesis, breakdown and storage Cartilage  Specialized for support, protection  Made of ______and elastic extracellular material  Serves as precursor for bone  Forms articular surfaces for joints Bone  Formed as concentric layers of calcified material  Contains 3 cell types:  Osteoblasts: bone-forming cells  Osteocytes: trapped, inactive osteoblasts  Osteoclasts: the bone ______cells Organs  Are anatomical and functional units made of two or more primary tissues  Systems are groups of organs working together to maintain homeostasis Skin  Has an outer layer of protective cornified ______ Next is dermis, which contains connective tissue, glands, blood vessels, nerves  Inner layer is hypodermis, which contains fat Stem Cells  Most cells in organs are highly specialized or ______ Many organs retain small populations of adult stem cells  less differentiated; can become many cell types Bone marrow stem cells can give rise to all of the different blood cell types Hair follicle stem cells can form the hair shaft, root sheath, sebaceous glands and epidermis</p><p>Body-Fluid compartments  Body has intracellular and extracellular compartments  Intracellular is inside cells  Extracellular is outside cells  Separated by cell’s outer membrane  Extracellular is composed of blood plasma and ______Chapter 2: Chemical Composition of the Body Atoms  Smallest units of the chemical elements  Has protons, ______and electrons  Nucleus contains protons (+ charge) and neutrons (no charge)  Electrons (- charge) occupy orbitals or shells outside nucleus  Atomic mass is sum of protons and neutrons in an atom  Atomic number is number of protons in an atom Electron Shells  Electron shells or orbitals are in layers around nucleus  Number of shells depends on atomic number  First shell can contain only 2 electrons  Second shell can contain up to 8 electrons  Electrons in more distant shells have higher energy  Valence electrons are those in ______shell  These can participate in chemical reactions and form bonds  Isotopes Are different forms of same atom  Atomic number is the same, but atomic mass is different  contain different numbers of neutrons Chemical Bonds  Molecules form by chemical bonding between valence electrons of atoms  Number of bonds determined by number of electrons needed to complete outermost shell Covalent Bonds  Occur when atoms ______valence electrons  In nonpolar covalent bonds electrons are shared equally  E.g. in H2 or O2  In polar bonds electrons are shared unequally  Pulled more toward one atom  Have + and – poles  Oxygen, nitrogen, phosphorous have strong pull  Tend to form polar molecules  E.g. H20 Ionic Bonds  Occur when valence electrons are transferred from one atom to another  Forming charged atoms (______)  Atom that loses electrons becomes a cation (+ charged )  Atom that gains electrons becomes an anion (- charged)  Ionic bonds are formed by attraction of + and - charges  Ionic bonds are weaker than polar covalents  ______when dissolved in H2O  Because H2O forms hydration spheres around ions  E.g. NaCl  Hydrophilic molecules are soluble in water  readily form hydration spheres  E.g. glucose and amino acids  Hydrophobic molecules are nonpolar, cannot form hydration spheres Hydrogen Bonds  When H forms polar bond, it takes on a slight + charge  It’s attracted to nearby negatively charged atoms  Called hydrogen bonds  Forms between adjacent H20s  Creating ______Acids and Bases  Acids release protons (H+) in a solution (proton donor)  Bases lower H+ levels of a solution (proton acceptor) pH  Is symbol for H+ concentration of a solution  pH scale runs from 0 to 14  pH = log 1/[H+]  Pure H2O is neutral and has pH = ______ Acids have a pH < 7 (pH 0 - 7)  Bases have a pH > 7 (pH 7 - 14) Buffers  Are molecules that slow changes in pH by either combining with or releasing H+s  E.g. the bicarbonate buffer system in blood:</p><p>H20 + C02 Ö H2C03 Ö H+ + HC03-</p><p> This buffers pH because reaction can go in either direction depending upon concentration of H+s Blood pH  Normal range of pH is 7.35 – 7.45  Maintained by buffering action  Acidosis occurs if pH < 7.35  Alkalosis occurs if pH > 7.45 Organic molecules  Are those that contain ______and hydrogen  Carbon has 4 electrons in outer shell  Bonds covalently to fill outer shell with 8 electrons  In body, carbons are linked to form chains or rings  Serve as “backbone” to which more reactive ______are added Functional groups:  Carbonyl group forms ketones and aldehydes  Hydroxyl group forms alcohols  Carboxyl group forms organic acids (lactic and acetic acids) Stereoisomers  Contain same atoms arranged in same sequence  Differ in spatial orientation of a functional group  D-isomers are right-handed  L-isomers are left-handed  Biological enzymes act on only 1 of stereoisomers  E.g., enzymes of all cells can use only L-amino acids and D-sugars Carbohydrates  Are organic molecules containing carbon, hydrogen and oxygen in ratio of CnH2nOn  Monosaccharides are simple sugars such as ______, fructose, galactose  Disaccharides are 2 monosaccharides joined covalently  Include:  Sucrose or table sugar (=glucose + fructose)  Lactose or milk sugar (=glucose + galactose)  Maltose or malt sugar (=2 glucoses)</p><p> Polysaccharides are many monosaccharides linked together  Include starch and glycogen, which are ______of thousands of glucoses  Energy storage molecules  Allows organisms to store thousands of glucoses in 1 polysaccharide molecule, which drastically reduces osmotic problems Formation of dissacharides  Occurs by splitting water out of 2 monosaccharides  An H+ and OH- are removed, producing H2O  Called ______or condensation Digestion of Polysaccharides  Is reverse of dehydration synthesis  H2O is split, H+ added to one monosaccharide, OH- to other -- called ______ Polysaccharide hydrolyzed into disaccharides, then to monosaccharides Lipids  Are insoluble in polar solvents such as water  ______ Consist primarily of hydrocarbon chains and rings Triglycerides  Formed by condensation of 1 glycerol and 3 fatty acids  Are ______if hydrocarbon chains of fatty acids are joined by single covalent bonds  Are unsaturated if there are double bonds within hydrocarbon chains Ketones Bodies  Hydrolysis of triglycerides releases free fatty acids  Which can be used for energy  Or converted in liver to ketone bodies  Which are acidic  High levels cause ketosis  Ketoacidosis occurs when ketone bodies in blood lower ______Phospholipids  Are lipids that contain a phosphate group  Phosphate part is polar and hydrophilic  Lipid part is nonpolar and hydrophobic  ______aggregate into micelles in water  Polar part interacts with water; nonpolar part is hidden in middle  Act as ______by reducing surface tension</p><p>Steroids  Are nonpolar and insoluble in water  Cholesterol is precursor for steroid hormones  Is component of cell membranes Prostaglandins  Are fatty acids with cyclic hydrocarbon group  Produced by and active in most tissues  Serve many regulatory functions Proteins-Amino Acids  Are made of long chains of amino acids  20 different amino acids can be used  Amino acids contain an amino group (NH2) at one end; ______group (COOH) at other end  Differences between amino acids are due to differences in functional groups (“R”) Proteins-Peptides  Are short chains of amino acids  Amino acids are linked by ______ Formed by dehydration reactions  If <100 amino acids, is called a polypeptide; >100 amino acids, is called a protein Proteins- Structure  Can be described at four levels  Primary structure is its sequence of amino acids  Secondary structure is caused by weak H bonding of amino acids  Results in alpha helix or beta pleated sheet shapes  Tertiary structure is caused by bending and folding of polypeptide chains to produce 3-dimensional shape  Formed and stabilized by weak bonds between functional groups  Not very stable; can be ______by heat, pH  Quaternary structure forms when a number of polypeptide chains are covalently joined  Many proteins are conjugated with other groups  Glycoproteins contain carbohydrates  Lipoproteins contain lipids  Others, like hemoglobin, contain a pigment Nucleic Acids  Include DNA and RNA  Are made of long chains of ______ Which consist of a 5-carbon sugar, phosphate group, and nitrogenous base  Bases are pyrimidines (1 ring) or purines (2 rings) Nucleic Acids – DNA  Contains genetic code  Its deoxyribose sugar (5C) is covalently bonded to 1 of 4 bases:  Guanine or adenine (purines)  Cytosine or thymine (pyrimidines)  Chain is formed by sugar of 1 nucleotide bonding to phosphate of another  Each base can form hydrogen bonds with other bases  This hydrogen bonding holds 2 strands of DNA together  The 2 strands of DNA twist to form a ______ Number of purines = pyrimidines  Due to law of complementary base pairing  adenine pairs only with thymine; cytosine with guanine Nucleic Acids – RNA  Consists of a long chain of nucleotides joined together by sugar-phosphate bonds  Its ribose sugar is bonded to 1 of 4 bases:  Guanine or adenine  Cytosine or ______(replaces thymine)  Single-stranded  3 types of RNA are synthesized from DNA and allow it to direct activities of a cell:  Messenger RNA - mRNA  Transfer RNA - tRNA  Ribosomal RNA - rRNA Chapter 3 Cell  Is the basic unit of structure and ______in body  Is a highly organized molecular factory  Has 3 main components: plasma membrane, cytoplasm and organelles Plasma Membrane  Surrounds and gives cell form; is ______permeable  Formed by a double layer of phospholipids  Which restricts passage of polar compounds  Proteins customize membranes  Provide structural support  Serve as ______, enzymes, receptors and identity markers  Carbohydrates (glycoproteins and glycolipids) are part of outer surface  Impart negative charge to surface  Serve as cell surface ______(antigens) Bulk Transport  Is way cells move large molecules and particles across plasma membrane  Some cells use ______to take in particulate matter  E.g. white blood cells and macrophages  Some cells use endocytosis to take in large compounds  Membrane invaginates to take in a vesicle of ______substance  Pinocytosis is non-specific intake  ______endocytosis uses receptors to take in specific compounds  Including some viruses  Cells use exocytosis to export products into the extracellular fluid  Via secretory vesicles Surface Specializations  Some epithelial cells have ______projecting from surface  Hair-like structures that beat in unison  Cilia line respiratory and reproductive tracts  Cilia contain microtubules  Some epithelial cells have microvilli on surface to increase surface area for absorption (Fig 3.6)  Finger-like structures that expand ______Cytoplasm and Cytoskeleton  Cytoplasm is the jellylike ______within a cell  Consists of fluidlike cytosol plus organelles  Cytoskeleton is a latticework of microfilaments and microtubules filling cytoplasm  Gives cell its ______ Forms tracks upon which things are transported around cell Organelles  Are cytoplasmic structures that perform specialized functions for cells Lysosomes  Are vesicle-like organelles containing ______enzymes  Involved in recycling cell components  Involved in programmed cell death Peroxisomes  Are vesicle-like organelles containing ______enzymes  Involved in detoxification in liver Mitochondria  Are ______-producing organelles  Believed to have originated from symbiotic bacteria ______ Are protein factories  Where cell's proteins are synthesized  Composed of 2 rRNA subunits Endoplasmic Reticulum  A system of membranes specialized for synthesis or degradation of molecules  Rough ER contains ribosomes for protein synthesis  Smooth ER contains enzymes for ______synthesis and inactivation Golgi Complex  Is a stack of flattened sacs  Vesicles enter from ER, contents are ______, and leave other side  Lysosomes and secretory vesicles are formed in Golgi Nucleus  Contains cell's ______ Enclosed by a double membrane nuclear envelope  Outer membrane is continuous with ER  ______complexes fuse inner and outer membranes together  Small molecules can diffuse through pore  Proteins, RNA must be actively transported Gene expression  Genes are lengths of DNA that code for synthesis of RNA  mRNA carries ______for how to make a protein  From the nucleus to ribosomes where proteins are made  Takes place in 2 stages:  Transcription occurs when DNA sequence in a gene is turned into a mRNA sequence  ______occurs when mRNA sequence is used to make a protein  Each nucleus contains 1 or more dark areas called ______ These contain genes actively making rRNA Genome and Proteome  Genome refers to all genes in an individual or in a species  ______refers to all proteins produced by a genome Chromatin  Is made of DNA and its associated positively charged proteins, ______ Each spool of histone and its DNA is called a nucleosome  Euchromatin is the part of ______active in transcription  Light in color  Heterochromatin is highly ______region where genes are permanently inactivated  Darker in color RNA Synthesis  One gene codes for one polypeptide chain  Each gene is several thousand nucleotide pairs long  For transcription, RNA ______binds to a “start” sequence on DNA and unzips strands  Transcription factors bind to “______” to initiate transcription  On the gene being transcribed  bases pair with complementary RNA bases to make mRNA  _____ pairs with C  A pairs with _____  RNA polymerase detaches when hits a "stop" sequence  Transcription produces four types of RNA:  pre-mRNA - altered in nucleus to form mRNA  mRNA - contains the code for synthesis of a protein  tRNA (transfer RNA) - ______the info contained in mRNA  rRNA - forms part of ribosomes  Pre-mRNA  Contains non-coding regions called ______ Coding regions are called exons  Introns are removed and ends of exons ______together to produce final mRNA  Human genome has <25,000 genes  Produces >100,000 different proteins  ______gene codes for an average of 3 different proteins  ______splicing of exons  Allows a given gene to produce several different mRNAs  New type of RNA regulates gene expression  Through RNA interference (RNAi) or ______ siRNA (short interfering RNA) and miRNA (micro RNA) molecules pair with different mRNAs  1 miRNA may ______with up to 200 different mRNAs Protein Synthesis  Occurs one amino acid at a time according to sequence of base ______in mRNA  In cytoplasm, mRNA attaches to ribosomes forming a polysome where translation occurs  Ribosomes read 3 mRNA bases (= a triplet) at a time  Each triplet is a ______, which specifies an amino acid  Ribosomes translate codons into an amino acid sequence that becomes a polypeptide chain  tRNA and enzymes translate codons  tRNA has 3 loops, one has an ______ Complementary to a specific mRNA codon  Each tRNA carries the amino acid specified by its anticodon  In a ribosome, anticodons on tRNA bind to mRNA codons  Amino acids on adjacent tRNAs are linked enzymatically by ______bonds  This forms a polypeptide; at a stop codon it detaches from ribosome Functions of ER  Proteins to be secreted are made in ribosomes of rough ER  Contain a ______sequence of 30+ hydrophobic aa that directs it into cisternae of ER  Where leader sequence is removed; protein is modified Functions of Golgi  Secretory proteins leave ER in ______and go to Golgi  In the Golgi complex carbohydrates are added to make glycoproteins  Vesicles leave Golgi for lysosomes or ______Protein Degradation  Many enzymes and regulatory proteins are controlled by rapidly degrading them  By ______in lysosomes  And by cytoplasmic proteasomes  Proteins are directed by ubiquitin tags DNA Replication  When cells divide, DNA replicates itself and identical copies go to 2 daughter cells  ______break hydrogen bonds to produce 2 free strands of DNA  DNA polymerase binds to each strand and makes new complementary copy of old strand  Using A-T, C-G pairing rules  Thus each copy is composed of 1 new strand and 1 old strand (______replication)  Original DNA sequence is preserved Cell Cycle  Most cells of body are in interphase - the non-dividing stage of life cycle  Interphase is subdivided into:  G1 - cell performs normal physiological roles  S - DNA is ______in preparation for division  G2 - chromatin condenses prior to division Cyclins  Are proteins that promote different phases of cell cycle  Overactivity of genes that code for cyclins is associated with cancer ______ Are genes whose mutations are associated with cancer  Tumor ______genes, like p53 inhibit cancer development  it encodes transcription factor  It halts cell division when DNA is damaged  and promotes DNA repair or apoptosis (cell ______)  Mutations in p53 are found in 50% of all cancers Cell Death  Occurs in 2 ways:  Necrosis occurs when pathological changes kill a cell  Apoptosis occurs as a normal physiological response  Also called programmed cell death  Involves activation of cytoplasmic ______, which lead to cell death Mitosis (M phase)  Is when cell divides  Chromosomes are condensed and duplicated  2 strands called ______ Which are connected by a centromere Consists of 4 stages: prophase, metaphase, anaphase, telophase  In prophase chromosomes become visible distinct structures  In ______chromosomes line up single file along equator  Positioned there by spindle fibers  In anaphase centromeres ______ Spindle fibers pull each chromatid to opposite poles  In telophase cytoplasm is divided (= cytokinesis), producing 2 daughter cells Role of Centrosome  All animal cells have a ______located near nucleus in interphase  Contains 2 centrioles  Centrosome is duplicated in G1  Replicates move to opposite poles by metaphase  Microtubules from centrosomes form ______fibers  Which attach to centromeres  Spindle fibers pull chromosomes to opposite poles during anaphase ______ Are non-coding regions of DNA at ends of chromosomes  Each time a cell divides, a length of telomere is lost  DNA polymerase can’t copy the very end of DNA strand  When telomere is used up, cell becomes ______with each division  Germinal and cancer cells can divide indefinitely and do not age  Have the enzyme telomerase which duplicates telomere nucleotides Meiosis  Is type of cell division occurring in ovaries and testes to produce ______(ova and sperm)  Has 2 divisional sequences - DNA is replicated once and divided ______ In 1st division, homologous chromosomes pair along equator of cell (singly in mitosis)  1 member of ______pair is pulled to each pole  Each daughter cell has 23 different chromosomes, consisting of 2 chromatids  In 2nd division each daughter chromosome splits into 2 chromatids  1 goes to each new daughter cell  Each daughter contains 23 chromosomes  Not 46 like mother cell  Meiosis is called ______ Genetic recombination occurs in prophase I  Parts of one homologous chromosome are exchanged with its partner homolog (= ______)  Provides tremendous genetic diversity Epigenetic Inheritance  Occurs when gene silencing is passed on to daughter cells  Gene silencing is enacted by DNA ______or post- translational modification of histones  Can contribute to diseases such as cancer, fragile X syndrome, and lupus Chapter 6 Extracellular Environment  Includes all constituents of body outside cells  67% of total body H2O is inside cells (=intracellular compartment); 33% is outside cells (=extracellular compartment-ECF)  20% of ECF is blood plasma  80% of ECF is ______contained in gel-like matrix Extracellular Matrix  Is a meshwork of collagen and elastin fibers  linked to molecules of gel-like ______substance and to plasma membrane integrins (adhesion molecules) Transport Across Plasma Membrane  Plasma membrane is ______--allows only certain kinds of molecules to pass  Carrier-mediated transport involves specific protein transporters  Non-carrier mediated transport occurs by diffusion  Passive transport moves compounds down concentration gradient; requires no energy  Active transport moves compounds ______a concentration gradient; requires energy and transporters Diffusion  Is random motion of molecules  Net movement is from region of ______concentration  Non-polar compounds readily diffuse thru cell membrane  Also some small molecules such as CO2 and H2O  Charged and most polar compounds  must have an ______or transporter to move across membrane  Rate of diffusion of a compound depends on:  Magnitude of its concentration gradient  Permeability of membrane to it  ______ Surface area of membrane Osmosis  Is net diffusion of H2O across a selectively permeable membrane  H2O diffuses down its concentration gradient  H2O is less concentrated where there are more solutes  Solutes have to be ______active  i.e., cannot freely move across membrane  H2O diffuses down its concentration gradient until its concentration is equal on both sides of a membrane  Some cells have water channels (aquaporins) to facilitate osmosis Osmotic Pressure  Is the force that would have to be exerted to ______osmosis  Indicates how strongly H2O wants to diffuse  Is proportional to solute concentration Molarity and molality  1 molar solution (1.0M) = 1 mole of solute dissolved in 1L of solution  Doesn't specify exact amount of H2O  1 molal solution (1.0m) = 1 mole of solute dissolved in 1 kg H2O  Osmolality (Osm) is total molality of a solution  E.g., 1.0m of NaCl yields a 2 Osm solution  Because NaCl dissociates into Na+ and Cl- Tonicity  Is the effect of a solution on osmotic ______of H2O  Isotonic solutions have same osmotic pressure  Hypertonic solutions have higher osmotic pressure and are osmotically active  Hypotonics have lower osmotic pressure  Isosmotic solutions have same osmolality as ______ Hypo-osmotic solutions have lower osmotic pressure than plasma  Hyperosmotics have higher pressure than plasma Regulation of Blood Osmolality  Blood osmolality is maintained in narrow range around 300mOsm  If dehydration occurs, osmoreceptors in ______stimulate:  ADH release  Which causes kidney to conserve H2O and thirst Carrier-Mediated Transport  Molecules too ______to diffuse are transported across membrane by protein carriers  Protein carriers exhibit:  Specificity for single molecule  Competition among substrates for transport  Saturation when all carriers are occupied  This is called Tm (transport maximum) Facilitated Diffusion Is passive transport ______concentration gradient by carrier proteins Active Transport  Is transport of molecules against a concentration gradient  ATP is required Na+/K+ Pump  Uses ATP to move 3 Na+ out and 2 K+ in  Against their gradients Secondary Active Transport  Requires ______to first move Na+ uphill to create a gradient  Secondary active transport then uses energy from “downhill” movement of Na+ to drive “uphill” transport of another molecule  ______(symport) is secondary transport in same direction as Na+  Countertransport (antiport) moves molecule in opposite direction to Na+ Transport Across Epithelial Membranes  Absorption is transport of digestion products across intestinal epithelium into blood  Reabsorption transports compounds out of urinary filtrate back into ______ Transcellular transport moves material from 1 side to other of epithelial cells  Paracellular transport moves material through tiny spaces ______epithelial cells  Transport between cells is limited by junctional complexes that connect adjacent epithelial cells  Plasma membranes join to form tight junctions  In adherens junctions membranes are “glued” by proteins crossing the membranes & attached to ______ In desmosomes proteins “button” two membranes together Bulk Transport  Moves ______molecules and particles across plasma membrane  Occurs by endocytosis and exocytosis Membrane Potential  Is difference in charge across membranes  Large anions are trapped inside cell  Cations like K+ are attracted into cell by anions  Na+ is not permeable and is ______transported out Equilibrium Potential Describes voltage across cell membrane if only 1 ion could diffuse  E.g. K+ would diffuse until it reaches its equilibrium potential (Ek)  K+ is attracted inside by anions but driven out by its concentration gradient  At K+ ______, electrical and diffusion forces are = and opposite  Inside of cell has a negative charge of about -90mV Nernst Equation (EX)  Gives membrane voltage needed to counteract concentration forces acting on an ion  Ex = 61 log [Xout] z [Xin] (z = valence of ion X) Resting Membrane Potential (RMP)  Is membrane voltage of cell not producing impulses  RMP of most cells is –65 to –85 mV  RMP depends on (1) conc of ions inside and out (2) ______of each ion  Affected most by K+, it is most permeable  Some Na+ diffuses in so RMP is less negative than EK+ Role of Na+/K+ Pumps in RMP  Because 3 Na+ are pumped out for every 2 K+ taken in, pump is electrogenic  It adds about –3mV to RMP Cell Signaling  Is how cells ______with each other  Some use gap junctions thru which signals pass directly from 1 cell to next  To respond to a chemical signal, a target cell must have a receptor protein for it  In paracrine signaling, cells secrete regulatory molecules that diffuse to nearby target cells  In synaptic signaling 1 neuron sends neurotransmitter messages to another cell via synapses  In endocrine signaling, cells secrete chemical ______that move thru blood stream to distant target cells How Regulatory Molecules Influence Target Cells  Nonpolar regulatory molecules pass through plasma membrane, bind to receptors in ______, and affect transcription  Examples include steroid and thyroid hormones and nitric oxide  Polar regulatory molecules bind to cell surface receptors  Activated receptors send ______messengers into cytoplasm to mediate actions of regulatory molecule Second Messengers  May be ions (e.g. Ca++) or other molecules such as cyclic AMP (cAMP) or G- proteins G-Proteins  Are part of 2nd messenger pathway in many cells  Contain 3 subunits whose components dissociate when a cell surface receptor is activated  A subunit binds to an ion channel or enzyme, changing their activity Chapter 12 Muscles Skeletal Muscles  Are attached to bone on each end by tendons  ______is the more movable attachment; is pulled toward origin-the less moveable attachment  Contracting muscles cause tension on tendons which move bones at a joint  Flexors decrease angle of joint  Extensors increase angle of joint  Prime mover of any skeletal movement is ______muscle  Antagonistic muscles are flexors and extensors that act on the same joint to produce opposite actions  Fibrous connective tissue from tendons forms sheaths (epimysium) inside and around skeletal muscle  Muscle is divided into columns called ______ Connective tissue around fascicles is called perimysium  Muscle fibers are muscle cells  Ensheathed by thin connective tissue layer called endomysium  Plasma membrane is called ______ Muscle fibers are similar to other cells except are multinucleate and striated  Most distinctive feature of skeletal muscle is its striations Neuromuscular Junction Includes the single synaptic ending of the motor neuron innervating each muscle fiber and underlying specializations of sarcolemma Place on sarcolemma where NMJ occurs is the ______Motor Unit  Each motor neuron branches to innervate a variable # of muscle fibers  A ______includes each motor neuron and all fibers it innervates. A motor neuron activates all muscle fibers in its motor unit  Innervation ratio is # motor neurons : muscle fibers  Vary from 1:100 to 1:2000  Fine control occurs when motor units are small, i.e. 1 motor neuron innervates small # of fibers  Individual motor units fire "all-or-none,"  Skeletal muscles perform smooth movements thru ______:  Brain estimates number of motor units required and stimulates them to contract  Keeps recruiting units until desired movement is accomplished in smooth fashion  More and larger motor units are activated to produce greater strength Structure of Muscle Fiber  Each fiber is packed with ______ Myofibrils are 1m in diameter and extend length of fiber  Packed with myofilaments  Myofilaments are composed of thick and thin filaments that give rise to bands which underlie striations</p><p>Structure of Myofibril  A band is dark, contains ______filaments (mostly myosin)  Light area at center of A band is ______ = area where actin and myosin don’t overlap  I band is light, contains thin filaments (mostly actin)  At center of I band is Z line/disc where actins attach Sarcomeres  Are ______units of skeletal muscle consisting of components between 2 Z discs  M lines are structural proteins that anchor myosin during contraction  ______is elastic protein attaching myosin to Z disc that contributes to elastic recoil of muscle Sliding Filament Theory of Contraction  Muscle contracts because myofibrils get shorter  Thin filaments ______over and between thick filaments towards center  Shortening distance from Z disc to Z disc  During contraction:  A bands (containing actin) move closer together, do not shorten  I bands shorten because they define distance between A bands of successive sarcomeres  H bands (containing myosin) ______Cross bridges  Are formed by heads of myosin molecules that extend toward and interact with actin  Each myosin head contains an ATP-binding site which functions as an ATPase  Myosin can’t bind to actin unless it is “cocked” by ATP  After binding, myosin undergoes conformational change (______) which exerts force on actin  After power stroke myosin detaches Control of Contraction  Control of cross bridge attachment to actin is via troponin-tropomyosin system  The filament tropomyosin lies in grove between double row of G-actins (actin thin filament)  Troponin complex is attached to tropomyosin at intervals of every 7 actins  In relaxed muscle, tropomyosin ______binding sites on actin so crossbridges can’t occur  This occurs when Ca++ levels are low (<10-6 M)  Contraction can occur only when binding sites are exposed Ca++ Control of Contraction  When Ca++ levels ______(>10-6 M), Ca++ binds to troponin causing conformational change which moves tropomyosin and exposes binding sites  Allowing crossbridges and contraction to occur  Crossbridge cycles stop when Ca++ levels decrease (<10-6 M)  Ca++ levels decrease because it is continually pumped back into the sarcoplasmic reticulum  Most Ca++ in SR is in ______ Running along terminal cisternae are T tubules Excitation-Contraction Coupling  Skeletal muscle sarcolemma conducts APs just like axons  Release of ______at NMJ depolarizes end-plate  APs race over sarcolemma and down into muscle via T tubules  T tubules are extensions of sarcolemma  Ca++ channels in SR are linked to T tubule channels  APs in T tubules cause release of Ca++ from cisternae via V-gated and Ca ++ release channels  Called ______release  channels are 10X larger than V-gated channels Muscle Relaxation  Ca++ from SR diffuses to troponin to initiate crossbridge cycling and contraction  When APs cease, muscle relaxes  Because Ca++ channels close and Ca++ is pumped back into SR Twitch, Summation, and Tetanus  A single rapid contraction and relaxation of muscle fibers is a ______ If 2nd stimulus occurs before muscle relaxes from 1st, the 2nd twitch will be greater (summation)  Contractions of varying strength (______contractions) are obtained by stimulation of varying numbers of fibers  If muscle is stimulated by an increasing frequency of electrical shocks, its tension will increase to a maximum (incomplete tetanus)  If frequency is so fast that no relaxation occurs, a smooth sustained contraction results called ______or tetany  If muscle is repeatedly stimulated with maximum voltage to produce individual twitches, successive twitches get larger  This is Treppe or staircase effect  Caused by accumulation of intracellular Ca++ Velocity of Contraction  For muscle to shorten it must generate force greater than the load  The lighter the load the ______the contraction and vice versa Isotonic, Isometric, and Eccentric Contractions  During isotonic contraction, force remains constant throughout shortening process  During isometric contraction, exerted force does not cause load to move and length of fibers remains ______ During eccentric contraction, load is greater than exerted force and fibers lengthen Length-Tension Relationship  Strength of muscle contraction influenced by:  Frequency of stimulation  ______of each muscle fiber  Initial length of muscle fiber  Ideal resting length is that which can generate maximum force  Too little overlap yields less tension because fewer cross bridges can form  With no overlap, no force generated because cross bridges cannot form Metabolism of Skeletal Muscles  Skeletal muscles respire ______1st 45-90 sec of moderate- to-heavy exercise  This is time to increase O2 supply to exercising muscles  Moderate exercise then uses aerobic respiration after two mins. Maximum Oxygen Uptake  ______(aerobic capacity) is maximum rate of oxygen consumption (V02 max)  Determined by age, gender, and size  Lactate (anaerobic) threshold is % of max O2 uptake at which there is significant rise in blood lactate levels  In healthy individuals this is at 50–70% V02 max Metabolism of Skeletal Muscles  During light exercise, most energy is derived from aerobic resp. of fatty acids  During moderate exercise, energy derived equally from fatty acids and glucose  During heavy exercise, ______supplies 2/3 of energy  Liver increases glycogenolysis  GLUT-4 carrier is moved to muscle cell’s plasma membrane Oxygen Debt  When exercise stops, rate of oxygen uptake does not immediately return to pre- exercise levels  Because of oxygen debt accumulated during exercise  O2 is withdrawn from hemoglobin and ______ O2 needed for metabolism of lactic acid from anaerobic respiration Phosphocreatinine  During exercise ATP is used faster than is generated by respiration  Phosphocreatine (creatine phosphate) is source of high energy Ps to regenerate ATP from ADP  Phosphocreatine levels are ______ATP Slow- and Fast- Twitch Fibers  Skeletal muscle fibers divided by contraction speed and resistance to fatigue:  Slow-twitch, slow fatigue (Type I fibers)  Fast-twitch, fast fatigue (Type IIA and IIX fibers)  ______due to slow or fast myosin ATPases Type I Fibers  Also called red slow oxidative  Adapted to contract slowly without fatiguing  Uses mostly aerobic respiration  Has rich capillary supply, many mitochondria, and aerobic enzymes  Has lots of myoglobin (O2 storage molecule)  Gives fibers ______color  Have small motor neurons with small motor units Type II Fibers  Type IIX fibers also called white fast glycolytic  Adapted to contract fast using anaerobic metabolism  Has large stores of ______, few capillaries and mitochondria, little myoglobin  Type II A fibers also called white fast oxidative  Adapted to contract fast using aerobic metabolism  Intermediate to Type I and Type IIX  Have large motor neurons with large motor units People vary genetically in proportion of fast- and slow-twitch fibers Muscle Fatigue  Is ______-induced reduction in ability of muscle to generate force  Due to accumulation of extracellular K+ during AP  Occurs in moderate exercise as slow-twitch fibers deplete glycogen stores  Fast twitch fibers are then recruited, converting glucose to lactic acid which interferes with Ca2+ transport  Central fatigue occurs as ______is less able to activate muscles even when muscle is not fatigued Adaptations Muscles to Exercise Training  Aerobic training improves aerobic capacity by 20% and lactate threshold by 30%  Weight training increases muscle size by increasing ______of myofibrils/fiber  And in some cases fibers can split Neural Control Skeletal Muscles  Motor neuron cell bodies are in ventral horn of spinal cord; axons leave in ventral root  Called lower motor neurons and final common pathway  Activity influenced by sensory ______from muscles and tendons Sensory Feedback  NS control skeletal muscle movements thru sensory feedback and  Information on tension from Golgi tendon organs  And on length of muscle from muscle spindle apparatus Muscle Spindle Appaeratus  Consists of modified thin muscle cells called ______fibers  Regular muscle fibers are extrafusal fibers  Spindles are arranged in parallel with extrafusals  Insert into tendons at each end of muscle  Intrafusal fibers have nuclei in ______region instead of contractile filaments  Nuclear bag fibers have nuclei arranged in loose aggregate  Nuclear chain fibers have nuclei arranged in rows  Nuclear bag and chain fibers are innervated by primary, annulospiral sensory endings  Which wrap around central regions  Respond most at onset of ______ Nuclear chain fibers additionally have secondary, flower-spray endings located at ends  Respond to sustained stretch  Both nuclear bag and chain fibers respond strongly to sudden, rapid stretching  Their activation causes a reflex contraction of muscle  Fast conducting ______innervate extrafusal fibers and cause muscle contraction  Slower conducting gamma motor neurons innervate and induce tension in intrafusal fibers (=active stretch)  Increases sensitivity of muscle to passive stretch Coactivation of Alpha and Gamma Motor Neurons  Upper motor neurons usually stimulate alpha and gamma motor neurons simultaneously (______)  Stimulation of alphas results in muscle contraction and shortening  Stimulation of gammas causes intrafusals to take up slack  Activity of gammas maintains normal muscle tone Monosynaptic-Stretch Reflex  Consists of only 1 synapse within CNS  Striking patellar ligament passively stretches spindles activating annulospiral sensory neurons  Which synapse on alphas causing them to stimulate ______ Produces knee-jerk reflex Golgi Tendon Organ Reflex  Involves 2 synapses in the CNS (=disynaptic reflex)  Sensory axons from Golgi tendon organ synapse on interneurons  Which make ______synapses on motor neurons  Prevents excessive muscle contraction or passive muscle stretching Reciprocal Innervation  Occurs in stretch reflexes because sensory neurons stimulate motor neuron and interneuron  Interneuron inhibits motor neurons of ______muscles  When limb is flexed, antagonistic extensors are inhibited from doing stretch reflex Crossed-Extensor Reflex  Involves double reciprocal innervation  Affecting muscles on ______side of cord  E.g. if step on tack, foot is withdrawn by contraction of flexors and relaxation of extensors  And contralateral leg extends to support body (crossed extensor reflex) Upper Motor Neuron Control of Skeletal Muscles  Influence lower motor neurons  Axons of neurons in precentral gyrus form ______tracts  Extrapyramidal tracts arise from neurons in other areas of brain  Cerebellum receives sensory input from spindles, Golgi tendon organs, and areas of cortex devoted to vision, hearing, and equilibrium  No descending tracts arise from cerebellum  Influences motor activity indirectly  All output from ______is inhibitory  Aids motor coordination  Basal ganglia exert inhibitory effects on activity of lower motor neurons Cardiac Muscle (Myocardium)  Contractile apparatus similar to skeletal  Striated and ______like skeletal but involuntary like smooth  Branched; adjacent myocardial cells joined by intercalated disks (gap junctions)  Allow APs to spread throughout cardiac muscle Smooth Muscle  Has no sarcomeres  Has gap junctions  Contains 16X more actin than myosin  Allows greater stretching and contracting  Actin filaments are anchored to ______bodies Smooth Muscle Contraction  Controlled by Ca++ but different from striated  Has little SR and no troponin/tropomyosin  Ca++ enters thru channels in plasma membrane  Binds with calmodulin  Ca++-calmodulin complex activates myosin light chain kinase (MLCK)  Which phosphorylates and ______myosin  Myosin forms crossbridges with actin  Relaxation occurs when Ca++ concentration decreases  Myosin is dephosphorylated  Myosin can no longer form crossbridges  Smooth muscle has ______contractions than striated  Can form a state of prolonged binding of myosin to actin (latch state)  Maintains force using little energy Single and Multiunit Smooth Muscle  Single unit is spontaneously active (myogenic)  Some cells are pacemakers  Has gap junctions to ______electrical activity  Multiunit requires nerve stimulation by ANS  NT released along a series of synapses called varicosities  Called synapses en passant (in passing)</p>