Topic 2 – Neuronal Physiology

Index

Topic 2 – Neuronal Physiology - Resting membrane potential - The NA+-K+ pump - Channels - Graded potentials - Action potentials - Voltage-gated channels o Voltage-gated Na+ channel o Voltage-gated K+ channel § Repolarisation § Depolarisation - Propagation of action potentials

Topic 3 – The Peripheral Nervous System - Efferent division o Somatic nervous system o Autonomic nervous system § Sympathetic nervous sysmte § Parasympathetic nervous system o Cholinergic neurons o Adrenergic neurons o Dominance o Rules about neurons o Neuromuscular junction o Comparison of a synapse and a neuromuscular junction

Topic 4 – Skeletal Muscle - General points - Organisation of a muscle - Thick filaments - Thin filaments o Actin o Tropomyosin o Troponin - Transverse tubular system (t-tubules) - Sarcoplasmic reticulum - Contraction of a skeletal muscle fibre - Filament slide switch - Muscle twitches o Amount of fibres o Amount of force o Twitch response o Twitch summation o Tetanic contraction o ATP and skeletal muscle contraction o Direct phosphorylation o Oxidative phosphorylation o Glycolysis

Topic 5 – Smooth Muscle - Similarities with skeletal muscle - Differences with skeletal muscle - Structure of smooth muscle - Dense bodies - Smooth muscle contraction ‘switch’ - Relaxation - Multi-unit smooth muscle - Single-unit smooth muscle o Pacemaker potentials o Slow-wave potentials

Topic 6 – Gastrointestinal Physiology - Processes o Mobility o Secretion o Digestion o Absorption - Digestive system composition o List of organs o Importance of ‘separation’ o Digestive tract composition - Regulation of digestive function o Autonomous smooth muscle function o Intrinsic nerve pulses o Extrinsic nerves o Gastrointestinal hormones - Receptors o Types of receptors o Types of neural reflexes - Tour of the digestive system o Salivary glands § Salivia § Salivation § Functions of saliva o Pharynx o Oesophagus § Swallowing § Oropharyngeal stage § Oesophageal stage § Gastro-oesophageal sphincter o Stomach § Structure § Functions § Motility • Gastric filling o Plasticity of smooth muscle o Receptive relaxation • Gastric storage • Gastric mixing • Gastric emptying o Factors in the stomach o Factors in the duodenum § Fat § Acid § Hypertonicity § Distension • Gastric digestive juices o Types of secretory cells o Mucus secretion o Pepsinogen secretion o HCI secretion o Intrinsic factor secretion o Gastrin secretion o Stomach reduction o Stomach ulcers o Absorption o Pancreatic and biliary secretions o Pancreas § Exocrine process • Enzymatic secretion o Trypsinogen o Chyymotrypsinogen o Procarboxypeptidase o Pancreatic Amylase o Pancreatic Lipase • Aqueous alkaline secretion o Biliary system § Composition § Bile salts § Sphincter of Oddi o Small intestine

Topic 7 – Endocrine Physiology - Hormones o Negative feedback control o Control of hormone release o Major endocrine organs o Other hormone producing structures o Disorders of the endocrine system § Hyposecretion • Causes • Treatment § Hypersecretion • Causes • Treatment - Absorptive state metabolism - Regulation of fuel metabolism o Pancreas § Islets of Langerhans • Insulin • Glucagon - Diabetes o Type I diabetes o Type II diabetes - Pituitary gland and hypothalamus o Posterior pituitary § Vasopressin § Oxytocin o Anterior pituitary and hypothalamus - Growth o Factors o Growth in children o Growth in soft tissue o Growth in bone o Abnormal secretion § Hyposecretion of growth hormone in children § Hyposecretion of growth hormone in adults § Hypersecretion of growth hormone in children § Hypersecretion of growth hormone in adults o Other essential growth hormones § Thyroid § Insulin § Androgen § Oestogen - Thyroid gland o Arrangement § Colloids and follicular cells § C cells o Synthesis of thyroid hormoens § Formation and storage of thyroglobulin § Iodine trapping and oxidation to iodine § Iodination § Coupling of T1 and T2 § Colloid endocytosis § Cleavage of hormones for release o Transport of thyroid hormones o Functions of the thyroid hormone § Effect on metabolic rate § Calorigenic effect § Intermediary metabolism § Sympathomimetic effect § Cardiovascular system § Growth and the nervous system o Regulation of thyroid hormone o Abnormalities of thyroid function § Hypothyroidism § Hyperthyroidism § Goiter - Parathyroid glands o Parathyroid hormone o Calcitonin

Topic 8 – Reproductive Physiology - Male reproductive system o Testes o Spermatogenesis o Spermatozoa o Sertoli cells o Control of testicular function o Accessory glands o Vasectomy - Female reproductive system o Ovaries o Oogenesis o Muturation of ova o Ovarian cycle § Follicular phase • Proliferation of granulosa cells • Formation of secondary follicles • Maturation of follicles (Graafian follicle) • Ovulation § Luteal phase • Non-fertilisation • Fertilisation o Hormonal control § Control of follicular function • FSH • LH § Control of the corpus luteum - Uterine changes linked to hormonal changes in the ovarian cycle o Uterus o Menstrual cycle § Menstrual Phase § Proliferation Phase § Secretory Phase o Contraception - Fertilisation o Oviduct o Transport of sperm o At the ovum o Development form fertilisation to implantation o Implantation o The placenta

Topic 2 – Neuronal Physiology

Resting Membrane Potential - Resting membrane potential is where excitable cells are not producing electrical signals - ALL plasma membranes have a membrane potential (i.e. are electrically polarized) - This can be one of two things… o The separation of opposite charges across the plasma membrane; OR o The differences in the relative number of cations in the ICF and ECF - This means that there is a slight excess of positive charges on the outside of the cell, and a slight excess of negative charges on the inside of the cell - Potential is measured in units of millivolts (mV), and as such a typical nerve cell has a membrane potential of -70mV - The cells of muscle and nerve cells are excitable cells i.e. they have the ability to produce rapid, transient changes in their membrane potential when excited - The ions primarily responsible for the resting membrane potential are… o NA+ – This is greater in concentration in the ECF o K+ – Much greater concentration in the ICF o A+

The magnitude of the potential depends on the degree of separation of the opposite charges The greater the number of charges separated, the larger the potential

The NA+ – K+ Pump - This pump establishes and maintains the concentration differences between NA+ and K+ at the expense of energy by essentially transporting the same number of K+ that had leaked out back into the cell, whilst simultaneously transporting the Na+ that leaked in - Inevitably this contributes to membrane potential… o 20%: Pumps 3 Na+ out for every 2 K+ transported in, resulting in more positive ions outside than inside the cell o 80%: The passive diffusion of K+ and Na+ down concentration gradients - NOTE: K+ has a much greater influence on the resting membrane potential than Na+

The Nerve/Muscle NA+ – K+ Pump Nerve and muscle cells have developed a specialized use for the membrane potential... - They are able to rapidly and transiently alter the permeability of their membranes to the ions involved to the appropriate stimulation, bringing about fluctuations in membrane potential - Rapid fluctuations in membrane potential are responsible for… o Producing nerve impulses in nerve cells o Triggering contraction in muscle cells

Terminology - Excitable Tissue: Capable of producing electrical signals when excited o Nerves: Use electrical signals to receive, process, initiate and transmit messages (i.e. the body’s messenger code’) o Muscles: Use electrical signals to ‘turn on’ the contractile process o There are two forms of electrical signal… § Graded Potential: These are SHORT distance signals § Action Potential: These are LONG distance signals - Electrical signals are created by the movement of ions through ion channels in the plasma membrane… o NOTE: The magnitude of potential is directly proportional to the number of positive and negative charges separated by the membrane o Polarization: The membrane has a potential; there is a separation of charge across the plasma membrane o Depolarization: The membrane potential becomes less polarized (i.e. less negative) than resting membrane potential o Repolarization: The membrane retuens to resting membrane potential after depolarization o Hyperpolarization: The membrane becomes more polarized (more negative) than resting membrane potential

Channels - The changes in the permeability of the plasma membrane to specific ions allows for ionic movement to be brought about - However, the ions responsible for carrying charge (that result in polarization) are water soluble and cannot penetrate the plasma membrane - As such, ions channels are required to move these ions across the plasma membrane; there are two types of ion channels… o Leak Channels: These are open all the time o Gated Channels: These can be open or closed in response to triggering events

Graded Potentials - These are local changes in membrane potential - Occur in varying degrees - Usually produced by a specific triggering event - Gated channels open in a specific part of the membrane - They cannot spread far from the area surrounding the site of stimulation o This is because the degree of depolarization decreases with distance because the cytosol offers considerable resistance to ion movement

ANY stimulus that opens a gated channel will produce a graded potential RULE: The stronger the triggering event, the more gated channels that open, the more positive charge that enters the cell, the larger the depolarizing graded potential at the point of origin

Action Potentials - An action potential is a brief, rapid, large change in membrane potential that is propagated along the membrane - The change is usually so large that for a brief period the inside of the cell becomes positive compared to the outside - It is used for LONG distance signals; they do not diminish in strength as they travel from their site of initiation to their site of impact - To initiate an action potential, a ‘triggering event’ causes the membrane to depolarize - If the ‘triggering event’ is sufficient enough to bring the cell to a charge of -50mV to -55mV, the ‘threshold potential’ will be reached o This results in an explosive depolarization, where the membrane potential becomes as high as +30mV o Subsequently, the potential then rapidly reverses and returns to resting levels (i.e. repolarization) - If the threshold is not reached no action potential will result o This is why the action potential are referred to as ‘all or nothing’ events; either the membrane is depolarized to threshold potential and an action potential takes place, OR the threshold is not reached in response to the triggering (depolarizing event) and no action potential occurs

How Membrane Potential is Thrown Outta Whack - Voltage-gated channels must open for changes in the membrane’s permeability to Na+ and K+ - When these channels open, rapid fluxes of these irons move down their electrochemical gradients - These ion movements carry a charge, and this charge is responsible for the changes in potential that occur during an action potential - There are two specific channels that are very important in the development of an action potential… o Voltage-gated Na+ channels o Voltage-gated K+ channels

Voltage-Gated Channels - Voltage: Open or close in response to changes in membrane potential - Gated: Gates that can be opened permitting the ion passage through the channel, OR gates that can be closed preventing ion passage through the channel - Voltage gated proteins are particularly sensitive to changes in voltage - Small distortions in channel shape induced by changes in potential can cause them to flip to another conformation (i.e. open or close)

Voltage-Gated Na+ Channel - This channel has TWO gates… o Activation Gate: This is like a hinged door in the sense that it allows the channel to open and close o Inactivation Gate: This is like a ball and chain; the gate is open when the ball is dangling, and the gate is closed when the ball finds its receptor located in the opening of the channel - To permit the passage of Na+ through this channel BOTH gates must be open; closure of either gate prevents Na+ movement

Voltage-Gated K+ Channel - This is comparatively simpler; it has ONE gate that can be open or closed

Repolarization - The membrane permeability to Na+ decreases dramatically, and no further entry of Na+ occurs

Depolarization - Na+ rushes into the cell carrying a positive charge with it - This depolarizes the membrane further causing more Na+ channels to opee, resulting in more Na+ moving into the cell o At this point, the membrane becomes 600 times more permeable to Na+ than K+ - Because of this, depolarization is a positive feedback system

Propagation of Action Potentials A neuron consists of three basic parts… - Cell Body – Houses the nucleus and organelles - Dendrites o Dendrites carry information TOWARDS the cell body o Protrudes from the cell body o Increases the surface area available for receiving signals from other nerve cell o One cell body can have as many as 400,000 dendrites - Axons o Is a single tubular extension of the cell body which carries information AWAY from the cell body o Once an action potential is triggered in the axon hillcock, no further triggering is necessary to activate the remainder of the fibre; this is because the impulse will be automatically conducted throughout the axon § The original action potential does not travel along the membrane; rather, it triggers an identical NEW action potential in an adjacent area of the membrane § Think of the Mexican wave; the wave moves, but individual spectators remain in the same position § NOTE: Action potentials are ALWAYS propagated at maximum amplitude

- Action potentials can only be initiated in portions of the membrane that have abundant voltage-gated Na+ channels - Sites specialized for graded potentials DO NOT undergo action potentials, even though the depolarization may be considerable (this is because there is not enough voltage-gated Na+ channels) - NOTE: Graded potentials can trigger action potentials - NOTE: Graded potentials can be summed

Direction of Propagation - Action potentials are ONLY propagated in ONE direction - This direction is always AWAY from the site of initiation

Refractory Periods - During a refractory period another action potential cannot be generated - The refractory period has two components… o Absolute Refractory Period: During the time when a patch of membrane is undergoing an action potential, it is not capable of initiating another action potential, no matter how strong the triggering event is o Relative Refractory Period: This follows the absolute refractory period. During this time, a second action potential can be produced ONLY if the triggering event is considerably stronger than usually necessary

How does the nervous system distinguish between two stimuli that both initiate an action potential but vary considerably in strength? - It does so with reference to the frequency with which the action potentials are generated - A stronger stimulus DOES NOT produce a larger action potential o However, it DOES trigger a greater number of action potentials per second to be propagated along the nerve fibre o As such, a stronger stimulus will cause more neurons to be brought to threshold thus increasing the total information sent to the CNS

Diameter of the Axon - When the fibre diameter increases, the resistance to current flow decreases - Therefore, the propagation of action potentials will be faster

Termination of an Action Potential A neuron can terminate on… - A muscle - A gland - Another neuron

Speed of Conduction The speed of an action potential depends on… - Whether the fibre is myelinated; and - The diameter of the axon

Myelination - An axon that is covered with myelin is called a myelinated fibre - Myelin is produced by… o Oligodendrocytes o Schwann cells - Myelin is interrupted at regular intervals in bare spots called the Nodes of Ranvier - Saltatory Conduction: Action potentials ‘skip’ or ‘jump’ from node to node along a myelinated axon