BB Lecture 16: Ligand-Gated Channels

Question 1

What is an excitatory stimulus?

Answer 1

one that depolarizes the membrane by

1. activating inward current
2. reducing outward current

Question 2

What is an inhibitory stimulus?

Answer 2

hyperpolarize the membrane by

1. increasing a K+ conductance
2. activating a Cl- conductance (decreases total membrane resistance)

Question 3

What are cys-loop channels? Provide examples

Answer 3

ligand-gated channels (activated by a ligand resulting in an inhibitory or excitatory stimulus)
selective for either cations or anions
each have two ligand binding sites that must be occupied for channel to open
Nicotinic acetylcholine receptor
GABA-A receptor

Question 4

What are glutamate receptors?

Answer 4

ligand-gated channels activated glutamate (ligand) to make an excitatory stimulus
mediate fast synaptic transmission in the brain
AMPA-type and NMDA-type

Question 5

What is the nAChR?

Answer 5

nicotinic acetylcholine receptor
two extracellular acetylcholine-binding sites
selective for cations (primarily to Na+ {inward} and K+ {outward} but can also allow Ca2+ and Mg2+) via rings of negatively charged residues lining outer regions of pore on both sides

Question 6

Describe the gating mechanism of ligand gated channels.

Answer 6

absence of ligand: M2 helices have hydrophobic kink directed into the pore to block channel
both binding sites occupied: M2 helices twist away from center of pore

Question 7

What is the GABA receptor?

Answer 7

ligand-gated channel
two binding sites for gamma-aminobutyric acid (GABA)
mediates fast inhibitory transmission in the brain
selective for anions (Cl- only) via ring of positively charged residues lining the pore

Question 8

What are AMPA-type glutamate receptors?

Answer 8

selective for Na+ and K+

requires glutamate binding to open

Question 9

What are NMDA-type glutamate receptors?

Answer 9

permeable to Na+, K+, and Ca2+
requires binding of glucose to open
also regulated by extracellular Mg2+ ion at resting Vm (must be expelled upon strong membrane depolarization)

Question 10

How do AMPA and NMDA glutamate receptors interact in neurons?

Answer 10

1. glutamate is released into synapse by activity of presynaptic neurons
2. glutamate crosses synapse and activates AMPA receptors
3. postsynaptic neuron is depolarized
4. Glutamate binds NMDA receptors to open the channel gate (Mg2+ is still blocking the channel at this time)
5. If presynaptic neurons are very active: surge of synaptic glutamate activates a large number of AMPA strongly depolarizing the cell and overcoming the Mg2+ ion
6. Ca2+ flows into postsynaptic neuron through NMDA activating enzymes to underlie the formation of memories