Ligand gated ion channels

What are ligand gated ion channels?

integral membrane receptor proteins which incorporate extracellular ligand binding sites and an ion channel

How does binding of the ligand lead to flow of ions?

binding of the ligand— conformational change in receptor— opening of ion pore— flow of ions in/out of cell down electrochemical gradient

How does ion flow lead to biological response?

modulation of cellular function

What are ligand gated ion channels involved in?

synaptic transmission, cell excitation, muscle contraction

Describe signal transduction via LGICs?

• extracellular messenger binds to receptor

• binding leads to opening of channel

• ions enter

• ion entry brings about result

What is receptor excitatory/inhibitory subclassification based on and what are the 2 types?

based on effect of membrane potential and electrical activity induced by ion flow of open channel.

excitatory causes membrane depolarisation

inhibitory causes membrane hyperpolarisation/

What are the subclassifications based on molecular structure and stoichiometry?

• cys-loop, 5 subunits

• ionitropic glutamate- 4 subunits

• P2X- 3 subunits

What are cys-loop LGICs activated by?

endogenously by acetylcholine and nicotine

Where does nAChR occur?

CNS and PNS and NMJ

How does binding of ACh lead to neurotransmitter release?

binding— channel opening — influx of Na+ ions— membrane depolarisation— influx of Ca++ and neurotransmitter release.

What are key functions of nAChRs in PNS?

autonomic system, skeletal contraction and control of peripheral organs

What key functions do nAChRs have in the CNS?

modulation of transmitter release, gene expression, cognition, memory formation

What are GABAa receptors and how are they activated?

cys-loop LGICs, by amino acid transmitter GABA.

How does GABA binding lead to post-synaptic inhibition?

GABA binding — channel opening— influx of Cl- ions— membrane hyperpolarisation— fast inhibition

Where do synaptic receptors occur?

post synaptically at synaptic sites

Where do extrasynaptic receptors occur?

post synaptically outside sites

Where are GABAa receptors most found?

cerebral cortex, hippocampus and cerebellum