Ligand Gated Ion Channels Flashcards
T/F: Ligand gated ion channels cannot initiate depolarization.
False
T/F: Ligand gated ion channels can have Excitatory Postsynaptic Potential (EPSP) or Inhibitory Postsynaptic Potential (IPSP)
True
Cholinergic Neurotransmitters
transmit Acetylcholine
Purine Neurotransmitters
transmit ATP
Biogenic Amine Neurotransmitters
transmit serotonin
Amino Acid Neurotransmitters
transmit Glutamate
transmit Glycine, GABA
Cationic channels affect EPSP or IPSP?
EPSP
Anionic channels affect EPSP or IPSP?
IPSP
Four examples of Cationic channels and what they transmit
- Cholinergic = acetylcholine
- purines = ATP
- biogenic amines = serotonin
- amino acids = glutamate
Example of anionic channels and what they transmit
amino acids = glycine, GABA
Purine Receptor Subunit
- P2X receptors
- nonselective cation channels
- cytosolic N & C termini w/ 1 extracellular loop (loop thought to contain ligand binding spot)
- widely distributed in CNS, PNS, and neuroglia
- may have role in neuropathic pain
Acetylcholine (nicotinic), GABAa, and Glycine Receptors
- 4 membrane spanning domains per subunit
- 5 subunits make 1 channel
- extracellular N & C termini
Subunits of nAch Receptors
- 2 alpha
- beta
- gamma
- delta
Subunits of GABAa Receptors
- 2 alpha
- 2 beta
- gamma
Subunits of Gly Receptors
- 3 alpha
- 2 beta
What is the primary inhibitory neurotransmitter in the brain and spinal cord?
GABA
What is the inhibitory neurotransmitter in the brain and spinal cord that affects antagonistic muscles?
Glycine
Glutamate Receptor subunits
- 3 transmembrane segments
- a predicted ‘P’ loop
- 4 or 5 subunits per channel
- All receptor types permeant to Na+ and K+
Nicotinic Acetylcholine Receptor shape
heteropentamer
possibilities of:
- alpha 1-9
- beta 1-4
- gamma
- delta
- epsilon
Subunits of an adult muscle nicotinic acetylcholine receptor
- 2 alpha
- beta 1
- gamma
- delta
Subunits of a neonatal muscle nicotinic acetylcholine receptor
- 2 alpha
- beta 1
- gamma
- epsilon
Subunits of a nerve nicotinic acetylcholine receptor
- 2 alpha
- 3 beta
Agonists of nAch Receptors
- nicotine
- carbamylcholine
- succinylcholine
- acetylcholine
- lemamisole
- pyrantel target helminth homolog
Antagonists of nAch Receptors
- trimethaphan
- alpha Bungarotoxin
- curare
What is responsible for binding to acetylcholine in nAch Receptors?
alpha subunits
Why is alpha Bungarotoxin considered functionally irreversible?
takes 20 minutes to release from binding site
not “real time” for physiological purposes
How many subunits are there per receptor for nAchR, GlyR, HT3R, and GABAa receptors?
5 subunits
Extracellular Subunit Topology
- Both N and C terminus
- consensus sites for glycosylation
- 2 cystine residues separated by 13 aa, that form a disulfide bond
- responsible for ligand binding
Transmembrane Subunit Topology
-4 segments (M1,M2,M3,M4)
In the transmembrane subunits, what is responsible for ion selectivity?
M2
M2 is contributed by each of the subunits forms aqeous pore/ ion channel.
Intracellular Subunit Topology
- responsible for intracellular processing, targeting, and anchoring
- natural mutations have occurred here and disease have been assoc. with these mutations
Do Glutamate and Purinergic receptors have the same topology as nAchR, GlyR, HT3R, and GABAa Receptors?
They do NOT share the same topology
How many subunits are there in serotonin HT3 Receptors?
5 - It’s a heteropentamer
A, B, C, D, and E exist
Agonist of serotonin HT3 Receptor
2-methyl serotonin
Antagonists of serotonin HT3 receptor
- Dolasetron
- Ondasetron
- Granisetron
- Palonosetron
- Alosetron (withdrawn)
nAchR, Receptor targeting, and anchoring
neuromuscular junction
[5 steps]
- Post-synaptic cell synthesizes rapsyn
- Rapsyn interacts with intracellular domain of nAchR
- At same time, nerves secrete agrin
- Agrin interacts with dystroglycan
- Rapsyn interacts with beta dystroglycan and with cytoskeleton
What does rapsyn do in regards to the neuromuscular junction?
causes clumping of receptors
What does agrin do in regards to the neuromuscular junction?
provides targeting cell for clumped receptors
T/F: Ligand-gated channels respond to chemical messenegers
True
What accounts for localization, activity, conductance, and pharmacology in many ligand-gated channels?
common structural motif
Acetylcholine- and serotonin-gated channels are _______ in nature.
excitatory
ie - strongly depolarizing
T/F: Ligand-gated channels provide examples of cooperativity and competitive and noncompetitive inhibition.
True
