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Ch 7 Part II Na+ linked symporters import amino acids and glucose into animal cells against high concentration gradients Operation Model for the two-Na+/one glucose symport Ch 7 part II Glucose transport against its gradient in the epithelial cells of intestine Na+ linked antiport Exports Ca+2 from cardiac Muscle Cells In cardiac or muscle, Ca2+ ↑→contraction Normal cytosol is 10000 fold of Ca2+ concentration than Cardiac (10-6 → 10-2 M) 烏本 毛地黃素 Cardiac muscles contain 3Na+/ 1 Ca2+ antiporter Movement of three sodium is required to power the export of one calcium + +2 + +2 3Na out+ Ca in 3Na in+ Ca out maintenance of low cytosolic Ca 2+ concentration i.e. inhibition of Na+/K+ ATPase by Quabain and Digoxin raises cytosolic Na+ Electrochemical gradient lowers the efficiency of Na+/Ca+2 antiport increases cytosolic Ca+2 More contraction ( used in cogestive heart failure) 1 Carrier proteins in the plasma membrane regulate cytosolic pH (pHi) at about 7.2 Cotransporters that regulate cytosolic pH + - H2CO3 H + HCO H+ can be neutrolized by 1.Na+/HCO3-/Cl- antiport 2. Cabonic anhydrase - - HCO3 CO2+OH 3. Na+/H+ antiport There are two mechanisms by which this pH is regulated -H+ is transported out of the cell Na+-H+ exchanger, an antiporter, couples the influx of Na+ to an efflux of H+ - + -HCO3 is brought into the cell to neutralize H in the cytosol + - - Na -driven Cl -HCO3 exchanger uses a combination The activity of membrane transport proteins that regulated the cytosolic pH of of the two mechanisms by coupling an influx of Na+ and memmalian cells changes with pH - + HCO3 to an efflux of Cl and H Plant vacuole membrane Numerous transport proteins enable plant Movement of water vacuoles to accumulate metabolites and • pH 3—6 Osmosis: movement of water across semipermeable ions • Low pH, maintained by membrane V-class ATP-powered pump Osmotic pressure: hydrostatic pressure uses to stop pyrophosphate-hydrolyzing proton pump (PPi -powered pump) the net flow of water 1 and 2 only presented in plant The H+ pump inside → inside positive → powers mover negative ion move inside; High positive inside When CB concentration > CA →antiport many ion and More positive sucrose → inward Osmotic pressure π=RT( CB-CA) 2 Hypertonic solution: the concentration is higher than cytosol 圓鋸齒 Isotonic solution: equal to cytosol Hypotonic solution: lower; and water move to cytosol Animal cell ace a problem in maintaining their cell volume within a limited range, thereby avoiding lysis Plant cell: has cell wall → prevent cell shape Turgor pressure (膨壓): osmotic pressure, plasma membrane against water into the cytosol and then into the vacuole turgor pressure supplies rigidity The large forces of turgor pressure are resisted by the strength of cellulose microfibrils in the cell wall Water channel protein ( aquaporin) Expression of aquaporin by frog oocytes increases their permeability Tetrameric protein Egg move to hypotonic environment •2-nm-long wate Injection aquaporin mRNA selective gate • 0.28nm gate width •Highly conserved arginine and histidine 6 α-helices for in the gate control each subunit • H O for HO bonding2 with cystein Aquaporin 1 erythrocyte 尿崩病 Aquaporin2 kidney cells resorb water from urine; mutation → diabetes insipidus → large volume urine 3 Trans-epithelial transport Import of molecules on the lumen side of intestinal Aquaporins are membrane water channels that play critical epithelial cells and their export on the blood facing sides roles in controlling the water contents of cells. Water crosses the hydrophobic membrane either by simple diffusion or through a facilitative transport mechanism mediated by these specialized proteins. These protein channels are widely distributed in all kingdoms of life, including bacteria, plants, and mammals. Important in osmotic regulation, acting to prevent bursting of the cells whenever there are changes of the exterior salt concentration. Transcellular transport of glucose from the intestinal lumen into the blood Parietal cells acidify the stomach contents while maintaining a neutral Glucose + normal saline → co-transport for energy supply cytolic pH 1 3 Acidification of the stomach lumen by parietal cells in the gastric lining 2 Basolateral Na+/ K+ ATPase generates Na+ gradient that 3 drives the Symporter 1 P-class Cholera toxin 4 activated by Cl- 2 4 Voltage-gate ion channels and the propagation of action potential in nerve cells Typical morphology of two types of mammalian neurons Neuron Action potential neurotransmitter 100m/sec • Cell body: • Axon: 軸突 – “Nutrition center.” • Axon terminal – Cell bodies within CNS clustered into nuclei, and in PNS • Dendrites: 樹突 in ganglia. • Myelin: 髓鞘 • Dendrites: • Neuron: 神經元 – Provide receptive area. • Node of Ranvier: 郎氏結 – Transmit electrical impulses to cell body. • Schwann cell: 許旺細胞 • Axon: • Synapse: 胞突 – Conducts impulses away from cell body. • Depolarization: 去極化 – Axoplasmic flow: • Repolarization: 再極化 • Proteins and other molecules are transported by rhythmic contractions to nerve endings. – Axonal transport: • Employs microtubules for transport. • May occur in orthograde or retrograde direction. 5 Action potential An action potential is triggered by a depolarization of the plasma membrane – that is, by a shift in the membrane potential to a less negative value Electrical vs Chemical Synapses Neurotransmitters Receptors ELECTRICAL (gap junction) CHEMICAL (synapse) 1. Ligand gated ion channels • 3.5 nm pre-post distance • 20-40 nm pre-post distance 2. G-protein coupled receptors • Cytoplasmic continuity (連續性) • No Cytoplasmic continuity • Gap-junction channels • Synaptic cleft (Ca2+ depend • Ion current neurotransmitter release) • No synaptic delay • Presynaptic vesicles and Synaptic vesicle: postsynaptic receptors • Bidirectional direction of • Chemical transmitter Storage of neurotransmitter. transmission • Smooth and cardiac muscles • 3 ms synaptic delay Low pH of vesicle lumen powers entry of • Unidirectional direction of neuritransmitter into lumen by H+/protein antipoter transmission • Functional connection between a neuron and another neuron (or effector cell such as muscle, gland) 6 Chemical synapse Gap junction Depolarization of the plasma membrane due to open of gated Na+ channel All cells maintain a resting membrane potential (RMP): – Potential voltage difference across membrane. • Largely the result of negatively charged organic molecules within the cell. • Limited diffusion of positively charged inorganic ions. – Permeability of cell membrane: • Electrochemical gradients of Na+ and K+. •Na+/K+ ATPase pump. Depolarization: Potential difference reduced (become more positive). Repolarization: Return to resting membrane potential (become more negative). Hyperpolarization: More negative than RMP 7 Voltage-gate Na+ channel is very sensitive channel For refractory peroid Voltage sensing Conformational changes underlying voltage sensing in AP are large and involve movements of arginine residues through the membrane, near the protein lipid interface Voltage gate sodium channel Voltage gated K+ channel (delayed K+ channel) Action potentials are propagated unidirectionally without diminution The “ball-and-chain” model of rapid inactivation for a voltage-gated K+ channel 8 All voltage-gate ion channels have similar structures Nerve cell can conduct many action potentials in the absence of ATP For voltage-gated channel Movement of the channel-inactivating segment into the open pore blocks ion flow No N-terminal ball Ball and chain model for inactivation of voltage-gated K+ channel Ball and Chain model for rapid inactivation of voltage-gated K Channels 9 Refractory Periods Action potential is generated when the membrane is locally During the time interval between the opening of the Na+ channel activation gate and the opening of the inactivation gate, a Na+ depolarized by ˜20 mV: channel CANNOT be stimulated. – This is the ABSOLUTE REFRACTORY PERIOD. Na+ goes in, K+ goes out – A Na+ channel cannot be involved in another AP until the inactivation gate has been reset. – This being said, can you determine why an AP is said to be unidirectional. For this process to occur, the voltage-gated channels should be: (a) highly selective c) voltage sensitive (b) very fast d) have a mechanism for rapid inactivation 10 Formation and structure of a myelin sheath in the peripheral nervous system Cross link Glial cells are also called neuroglia or supporting cells. Glial cells CNS glial cells Oligodendrocytes: – - form myelin sheaths around several axons. • 100 billion neurons – occur mostly postnatally. Nodes of Ranvier: • 10x more glial cells! - - unmyelinated areas of the axon located between adjacent oligodendrocytes (or Schwann cells) • Glial cells: - - action potential takes place here - - Support neurons (physically, and nutrients) PNS Supporting Cells Schwann cells: - - Cover neurons with myelin – - form myelin sheath around one axon - - Clean up debris – Nodes of Ranvier: – - unmyelinated areas of the axon located between - “housewives?” and … who is in “control?!” adjacent Schwann cells (or oligodendrocytes) – - action potential takes place here 11 Action potentials jump from node to node in myelinate axons Continuous vs. saltatory conduction Neurotransmitter and receptor and transport proteins in signal MS (multiple sclerosis) transmission at synapses Neurotransmitter Demyelinating disease packaged → synaptic vesicles → axon terminus → presynaptic cell→ release → bond to receptor → removed by enzyme or transport 12 Exocytosis of synaptic vesicle Cycling of nuerotransmitters
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