PSC2002/L14 Ligand Gated Channels Flashcards
Define neurotransmitters.
Chemical messengers released from one neuron and acting at a close site on another to elicit an effect determined by the specific nature of the receptor
What is acetylcholine for?
Voluntary movement of muscles
What is glutamate used for?
Major excitatory neurotransmitter
Roles in memory & learning
What is dopamine for?
Motivation
Pleasure associated with addiction & love
What is serotonin for?
Emotions, wakefulness
Temperature regulation
What is GABA for?
Major inhibitory neurotransmitter
What is ATP for?
Neuronal/glial communication, role in pain regulation
Define endogenous agonists.
Ligands made in the body which cause a postsynaptic effect
Describe ionotropic receptors.
Ligand-gated ion channels
Binding of neurotransmitter triggers opening of channel
Quickly changes electrical charge of a cell
Describe metabotropic receptors.
GPCR
G-protein phosphorylation pathway
cAMP, IP3 or DAG
How are ion channels best understood?
In terms of their reverse potentials
Name 2 non-specific cation channels.
E(AChR)
E(glut)
Describe synaptic transmission of ACh. (4)
Synthesis in cytoplasm by ChAT combining acetyl-CoA with choline
Depolarisation - AP reaches axon terminal
Calcium influx via VG Ca2+ channels
Vesicle fusion - release of ACh
Binding to ionotropic & metabotropic receptors
Describe termination of ACh action.
AChE breaks down ACh into acetate and choline
Choline reuptake via choline transporter into postsynaptic membrane
Describe recycling & resynthesis of ACh.
Choline combined with acetyl-CoA in presynaptic neuron to form more ACh
Describe Loewi’s experiment (1936). (3)
2 frog heart preps with interconnected perfusion chambers
Stimulated one vagal nerve to slow heart rate
Effect also transferred to second heart
Define a quanta.
Contents of one vesicle of neurotransmitter
How does the smallest postsynaptic response arise?
From release of one vesicle’s contents
What is a mini?
Postsynaptic response of a single vesicle released spontaneously
Describe the evidence in termination of ACh transmission.
Persistent ACh application produces persistent current (not indefinitely; AChRs desensitise)
Q(10) - diffusion dominated processes have Q(10) = ~1
Voltage dependence of decay (faster at more negative holding potentials)
Describe Neher and Sakmann’s patch clamping experiment. (3)
Glass pipette with fine tip to isolate and seal small patch of membrane
Pipette gently pressed against cell membrane, strong enough seal = tight connection (high-resistance seal
Measures small currents through ion channels without significant leakage or noise from rest of cell
Where are nicotinic ACh receptors found?
NMJ (muscle cells)
Between pre & postsynaptic cells in ANS
What are nicotinic ACh receptors permeable to?
Na+
K+
Ca2+
E(rev) = ~5mV
What is the composition of nicotinic ACh receptors? Which subunit binds ACh?
2a, 1B, 1d, 1E
a subunits binds ACh (2 ACh bind per receptor)
Give 2 antagonists of the nicotinic ACh receptor.
a-bungarotoxin (snake venom)
Curare compounds (plants)
Describe myasthenia gravis and what 2nd subset is.
Autoimmune disease
Body produces autoantibodies against nicotinic ACh receptors
Membrane damage & decreased availability & number of AChRs
2nd subset - autoantibodies against Muscle Specific Kinase (MuSK)
Which GABA and glycine receptors are:
a) ionotropic
b) metabotropic?
a) GABA(A&C), glycine
b) GABA(B)
When are E(cl) and E(m) inhibitory?
Below action potential threshold (as they’re close together)
Describe 5HT(3) receptors.
Pentamers
Similar transmembrane loops
Na+, K+, Ca2+ permeability (other 5HT-Rs are metabotropic)
What is dictated by subunit composition in GABA-R? (3)
Receptor properties (sensitivity, conductance, kinetics of opening and closing)
Cell surface distribution
Dynamic regulation
Describe the Met286 to Trp (BM286W) mutation to GABA(A) receptors.
Abolition of pentobarbital sensitivity of B2 receptor channel
In wild-type B2 receptor channel, markedly increased by coapplication of GABA and pentobarbital
Describe modulation of synaptic receptors. (3)
Benzodiazepines (e.g., diazepam)
Mediate sedation
Bind at interface of a/y2 subunits
Describe modulation of extrasynaptic receptors. (3)
Barbituates increase affinity of GABA
Neurosteroids both positive and negative allosteric modulation
Alcohol enhances GABA action
Describe pharmacological modulation of GABA-Rs.
Modulators of GABAergic action
Make distinction between agonists and some drugs.
What is the purpose of:
a) barituates
b) benzodiazepines?
a) ‘locks’ GABA receptors in open state
b) eases opening of receptors
Describe P2X ionotropic receptor.
ATP agonist
Different structure to other channels
Na+, K+, Ca2+ permeable
Widespread glia and neuronal expression
ATP released in synaptic vesicles
Important means of neuronal to glial, glia-to-glia communication
