L8: Ligand-Gated Ion Channels Flashcards
(34 cards)
Describe ligand-gated ion channels in terms of timescale, effector and coupling. Give examples
Timescale: milliseconds
Effector: channels
Coupling: direct
Example: nicotinic AChR; GABAa receptor; NMDA
mediator of fast synaptic transmission
Why do Ligand-gated ion channels need to be tightly regulated?
- too much inhibition can result in loss of consciousness
- too much excitation can result in seizures
What are the members of Cys Loop family of LGICs?
LGICs receptors of Cys Loop family:
- muscle nicotinic
- neuronal nicotinic
- GABAa
- Glycine
- 5-HT3
On what receptors and where does ACh act?
- on muscle nicotinic in endplate
- on neuronal nicotinic in autonomic ganglia, CNS
On what receptors and where does GABA act?
on GABAa receptors in CNS (brain)
On what receptors and where does glycine act? Inhibitory or excitatory?
on glycine receptors in CNS (spinal cord, brainstem); inhibitory
On what receptors and where does 5-HT act?
on 5-HT3 in CNS, periphery
On what receptors and where does glutamate act?
- on NMDA receptors in CNS
- on AMPA receptors in CNS
- on kainate receptors in CNS
On what receptors and where does ATP act?
on P2X receptors in CNS, periphery
To which ions are muscle and neuronal nicotinic LGICs permeable, what’s their nature of action?
- muscle nicotinic to Na+, K+
-
neuronal nicotinic Na+, K+, Ca2+
they’re both excitatory (depolarisation)
To which ions are GABAa and Glycine LGICs permeable, what’s their nature of action?
They’re both permeable to Cl- and are inhibitory
To which ions are 5-HT3 LGICs permeable, what’s their nature of action?
To Na+, K+ and is excitatory (depolarisation)
To which ions are NMDA, AMPA and kainate LGICs permeable, what’s their nature of action?
to Na+, K+, Ca2+, they’re all excitatory (depolarisation)
Describe Cys-loop type LGICs and give examples
- pentameric assembly
- 4 TM domains
- long cys-loop
- TM2 lining the ion channel pore
examples: nAChR, GABAa, 5-HT3
Describe Ionotropic glutamate type LGICs and give examples
- tetrameric assembly
- 3 TM domains
- hairpin loop
example: NMDA
Describe P2X type LGICs and give examples
- trimeric assembly
- 2 TM domains
example: P2XR
Describe Calcium release type LGICs and give examples
- tetrameric assembly
- 6 TM domains
- hairpin loop
example: IP3R
Describe nAChRs
- pentameric
- 4 transmembrane domains (alpha-helices)
- TM2 lines the ion channel pore
- acetylcholine binds only in between alpha-gamma and alpha-sigma regions
- forms Cys-loop
- homology between the same subunit across species is very high (50-90%)
How many transmembrane domains do nAChRs constitute of?
4 transmembrane domains
Which transmembrane domain lines the nAChR ion channel pore? What’s the charge of it?
TM2, negative charge, cationic channel
In between which regions does ACh bind in nAChRs?
acetylcholine binds only in between alpha-gamma (alpha-epsillon in adults) and alpha-sigma regions
In between which transmembrane domains is this large Cys loop of nAChRs located?
Large intracellular loop between TM3 and TM4
What is the importance of the Cys loop in nAChRs?
Key component in terms of ligand binding
Where are muscle type and neuronal type nAChRs located?
- muscle type: neuromuscular junction
- neuronal type: autonomic ganglia, synapses within the CNS
