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Gated Ion Channels

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Gated Ion Channels Ahu Karademir Andrei Vasiliev Contents General Information Voltage-Gated Ion Channels Ligand-Gated Ion Channels The Acetylcholine Receptor ... – PowerPoint PPT presentation

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Title: Gated Ion Channels


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

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8
What gates ion channels?
  • Non gated - always open
  • Gated
  • ?? Voltage across the cell membrane
  • ?? Ligand
  • ?? Mechanical stimulus, heat (thermal
    fluctuations)

9
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

10
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

11
Voltage-gated cation channels -function
  • Na and K
  • -Action potential
  • Ca2
  • -Secretion
  • -Signaling
  • -Muscle contraction
  • -Gene expression

12
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

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14
How does the Na channel open and close?
15
Voltage- gated Na channels
  • One large polypeptide of four domains
  • Responsible for depolarization phase of action
    potential
  • Target for local anesthetics
  • -Inactivation

16
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

17
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

18
Ligand gated channels
  • Glutamate receptors
  • Nicotinic acetylcholine receptor
  • Vanilloid receptor family (TRPV)

Ion Flow Current
Neurotransmitter
19
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

20
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 (or e)
d
ACh
21
The ACh receptor also responds to nicotine, and
so is called the nicotinic acetylcholine
receptor -nAChR
22
Acetylcholine Receptor
23
Nicotinic Acetylcholine Receptor A ligand
gated ion channel
24
the resting (closed) ion channel to acetylcholine
(ACh)produces the excited (open) state. Longer
exposure leads to desensitization and channel
closure.
Acetylcholine binding sites
Continued excitation
Na, Ca2
ACh
Outside
Inside
Desensitized (gate closed)
Resting (gate closed)
Excited (gate open)
ACh
25
Synaptic transmission throughout the nervous
system is predominantly Chemical At the
chemical level, the key players include integral
membrane proteins that control signaling
26
Neurotransmission is fast and precise Action
Potential opens voltage gated Ca2 channels
Ca2 enters the terminal. Ca2 initiates
vesicular release of neurotransmitter
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28
Mechanism of Transmitter release
Reserve vesicles are outside the active zone.
Synapsins tethers vesicles to the
cytoskeleton Ca2 activates Ca2/calmodulin
dependent protein kinase which phosphorylates
synapsin I and frees the vesicles.
29
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30
Toxins Target Ion Channels
  • Neurotoxins produced by many organisms attack
    neuronal ion channels,
  • fast-acting
  • deadly

31
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