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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 Neurotransmitters Toxin targets. Gated Ion Channels. Another type of membrane transport

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gated ion channels

Gated Ion Channels

Ahu Karademir

Andrei Vasiliev

contents
Contents
  • General Information
  • Voltage-Gated Ion Channels
  • Ligand-Gated Ion Channels
  • The Acetylcholine Receptor
  • Neurotransmitters
  • Toxin targets
gated ion channels3
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

gated ion channels4
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
ion channels are everywhere
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

gating mechanisms
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
what gates ion channels
What gates ion channels?
  • Non gated - always open
  • Gated

􀁺 Voltage across the cell membrane

􀁺 Ligand

􀁺 Mechanical stimulus, heat (thermal fluctuations)

gating mechanisms9
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
voltage gated cation channels
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
voltage gated cation channels function
Voltage-gated cation channels -function
  • Na+ and K+

-Action potential

  • Ca2+

-Secretion

-Signaling

-Muscle contraction

-Gene expression

voltage gated cation channels structure
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
voltage gated na channels
Voltage- gated Na+ channels
  • One large polypeptide of four domains
  • Responsible for depolarization phase of action potential
  • Target for local anesthetics

-Inactivation

voltage gated ca2 channels
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

voltage gated ca2 channels17
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
ligand gated channels
Ligand gated channels
  • Glutamate receptors
  • Nicotinic acetylcholine receptor
  • Vanilloid receptor family (TRPV)

Ion Flow = Current

= Neurotransmitter

ligand gated ion channels
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
acetylcholine receptor
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

slide21

The ACh receptor also responds to

nicotine, and so is called the “nicotinic” acetylcholine receptor -nAChR

slide24

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

slide25

•Synaptic transmission throughout the nervous system is predominantly

Chemical

•At the chemical level, the key players include integral membrane

proteins that control signaling

slide26

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

mechanism of transmitter release
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.

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