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Gated Ion Channels

Gated Ion Channels

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Gated Ion Channels

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  1. Gated Ion Channels Ahu Karademir Andrei Vasiliev

  2. Contents • General Information • Voltage-Gated Ion Channels • Ligand-Gated Ion Channels • The Acetylcholine Receptor • Neurotransmitters • Toxin targets

  3. Gated Ion Channels • Another type of membrane transport • Pores in the membrane that open and close in a regulated manner and allow passage of ions -“Dispose” of the gradients • Passive transporters -Ions flow from high to low concentration -No energy is used -If there is no gradient ions will not flow

  4. Gated Ion Channels • Small highly selective pores in the cell membrane • Move ions or water • Fast rate of transport 107 ions/s • Transport is always down the gradient • Can not be coupled to the energy source

  5. Ion channels are everywhere • Channels are present in almost every cell • Functions -Transport of ions and water -Regulation of electrical potential across the membrane -Signaling

  6. Gating mechanisms • Two discrete states ;open (conducting) closed (nonconducting) • Some channels have also inactivated state (open but nonconducting) • Part of the channel structure or external particle blocks otherwise open channel

  7. What gates ion channels? • Non gated - always open • Gated 􀁺 Voltage across the cell membrane 􀁺 Ligand 􀁺 Mechanical stimulus, heat (thermal fluctuations)

  8. Gating mechanisms • Conformational changes in channel protein are responsible for opening and closing of the pore -3D conformational shape is determined by atomic, electric, and hydrophobic forces • Energy to switch the channel protein from one conformational shape to another comes from the gating source

  9. Voltage-gated cation channels • Open in response to changes in membrane potential • Subsequently open and inactivate • Specific for a particular ion • Common domain structure • Regulated by external signals

  10. Voltage-gated cation channels -function • Na+ and K+ -Action potential • Ca2+ -Secretion -Signaling -Muscle contraction -Gene expression

  11. Voltage-gated cation channels -structure • Contain four subunits each containing six transmembrane segments • K+ is a tetramer • Na+ and Ca2+ 4 polypeptides are connected into one chain

  12. How does the Na+ channel open and close?

  13. Voltage- gated Na+ channels • One large polypeptide of four domains • Responsible for depolarization phase of action potential • Target for local anesthetics -Inactivation

  14. Voltage - gated Ca2+ channels • One large polypeptide of four domains • Heavily regulated by cell surface receptors -Have the place for the direct interaction with G proteins and phosphorylation • Responsible for ALL secretion -Presynaptic terminal and all secretory cells

  15. Voltage - gated Ca2+ channels • In neurons mostly responsible for the entry of calcium into the presynaptic ending following depolarization (and subsequent exocytosis of neurotransmitter) • In heart excitation contraction coupling • In all excitable secretory cells (adrenal medulla, pancreas) entry of calcium induces secretion

  16. Ligand gated channels • Glutamate receptors • Nicotinic acetylcholine receptor • Vanilloid receptor family (TRPV) Ion Flow = Current = Neurotransmitter

  17. Ligand gated ion channels • Gated by ligands present outside of the cell • In fact they are receptors • All of them are nonselective cation channels • Mediate effects of neurotransmitters

  18. Acetylcholine Receptor • consists of a pentamer of protein subunits, with two binding sites for acetylcholine, which, when bound, alter the receptor's configuration and cause an internal pore to open. • This pore allows Na+ ions to flow down their electrochemical gradient into the cell. a b ACh g (ore) d ACh

  19. The ACh receptor also responds to nicotine, and so is called the “nicotinic” acetylcholine receptor -nAChR

  20. Acetylcholine Receptor

  21. Nicotinic Acetylcholine Receptor A ligand gated ion channel

  22. the resting (closed) ion channel to acetylcholine (ACh)producesthe excited (open) state. Longer exposure leads to desensitization and channel closure. Acetylcholine binding sites Continued excitation Na, Ca2 ACh Outside Inside Resting (gate closed) Desensitized (gate closed) Excited (gate open) ACh

  23. •Synaptic transmission throughout the nervous system is predominantly Chemical •At the chemical level, the key players include integral membrane proteins that control signaling

  24. Neurotransmission is fast and precise Action Potential opens voltage gated Ca+2 channels Ca+2 enters the terminal. Ca+2 initiates vesicular release of neurotransmitter

  25. Mechanism of Transmitter release Reserve vesicles are outside the active zone. Synapsins tethers vesicles to the cytoskeleton Ca+2 activates Ca2+/calmodulin dependent protein kinase which phosphorylates synapsin I and frees the vesicles.

  26. Toxins Target Ion Channels • Neurotoxins produced by many organisms attack neuronal ion channels, • fast-acting • deadly