Title: Gated Ion Channels
1Gated Ion Channels
- Ahu Karademir
- Andrei Vasiliev
2Contents
- General Information
- Voltage-Gated Ion Channels
- Ligand-Gated Ion Channels
- The Acetylcholine Receptor
- Neurotransmitters
- Toxin targets
3Gated 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
4Gated 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
5Ion channels are everywhere
- Channels are present in almost every cell
- Functions
- -Transport of ions and water
- -Regulation of electrical
- potential across the
- membrane
- -Signaling
6Gating 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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8What gates ion channels?
- Non gated - always open
- Gated
- ?? Voltage across the cell membrane
- ?? Ligand
- ?? Mechanical stimulus, heat (thermal
fluctuations)
9Gating 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
10Voltage-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
11Voltage-gated cation channels -function
- Na and K
- -Action potential
- Ca2
- -Secretion
- -Signaling
- -Muscle contraction
- -Gene expression
12Voltage-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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14How does the Na channel open and close?
15Voltage- gated Na channels
- One large polypeptide of four domains
- Responsible for depolarization phase of action
potential - Target for local anesthetics
- -Inactivation
16Voltage - 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
17Voltage - 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
18Ligand gated channels
- Glutamate receptors
- Nicotinic acetylcholine receptor
- Vanilloid receptor family (TRPV)
Ion Flow Current
Neurotransmitter
19Ligand 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
20Acetylcholine 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
21The ACh receptor also responds to nicotine, and
so is called the nicotinic acetylcholine
receptor -nAChR
22Acetylcholine Receptor
23Nicotinic Acetylcholine Receptor A ligand
gated ion channel
24the 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
25Synaptic transmission throughout the nervous
system is predominantly Chemical At the
chemical level, the key players include integral
membrane proteins that control signaling
26Neurotransmission 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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28Mechanism 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.
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30Toxins Target Ion Channels
- Neurotoxins produced by many organisms attack
neuronal ion channels, - fast-acting
- deadly
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