Diazepam (Valium) is a benzodiazepine that produces calming effects by acting on GABA-A receptors. How does diazepam work?
ADiazepam mimics GABA, binding to the GABA site and directly opening chloride channels
BDiazepam binds an allosteric site on the GABA-A receptor, increasing the frequency of channel opening when GABA is present
CDiazepam blocks glutamate receptors on the same neuron, reducing excitatory input
DDiazepam increases GABA synthesis and release from presynaptic terminals
Diazepam is an allosteric modulator, not a GABA mimic. It binds a site distinct from the GABA binding site and increases how often the channel opens in response to GABA — it does not open the channel on its own. This distinction matters: allosteric modulators fine-tune receptor responsiveness without replacing the neurotransmitter. This is also why benzodiazepines are relatively safe at moderate doses — they require endogenous GABA to have an effect, creating a natural ceiling.
Question 2 Multiple Choice
A researcher applies a saturating concentration of glutamate to a preparation of AMPA receptors and observes that some channels remain closed at any given instant. The best explanation is:
AAMPA receptors require a co-agonist in addition to glutamate to open
BGlutamate failed to fully saturate all binding sites at the concentration used
CLigand binding shifts the probability of channel opening but channels gate stochastically — even with ligand bound, channels can be in a closed state at any moment
DAMPA receptors have entered a desensitized state, which is triggered by low glutamate concentrations
Ligand-gated channels are probabilistic, not deterministic. Neurotransmitter binding shifts the equilibrium from 'mostly closed' to 'more likely open,' but channels flicker between open and closed states continuously. Even with saturating ligand concentration, a proportion of channels will be closed at any instant. This probabilistic gating is a fundamental property of membrane proteins — not a failure of ligand binding.
Question 3 True / False
GABA-A receptors produce inhibitory postsynaptic potentials (IPSPs) by allowing chloride ions to flow into the cell, hyperpolarizing the membrane.
TTrue
FFalse
Answer: True
The chloride equilibrium potential is typically around −70 mV — near or slightly below the resting membrane potential. When GABA-A channels open and Cl⁻ flows in (down its electrochemical gradient), the membrane potential is driven toward this value, opposing depolarization toward the action potential threshold. This makes GABA-A activation inhibitory: it either hyperpolarizes the neuron or clamps the membrane potential near rest, both of which reduce the likelihood of firing.
Question 4 True / False
Most ligand-gated ion channels produce excitatory effects because neurotransmitter binding causes channel opening, which typically depolarizes the membrane.
TTrue
FFalse
Answer: False
Whether a ligand-gated channel is excitatory or inhibitory depends on which ions flow through it, not merely on the fact that it opens. GABA-A and glycine receptors are anion channels: they pass chloride (Cl⁻) inward, driving the membrane potential negative — an inhibitory effect. Excitatory effects (EPSPs) occur only when cation channels (sodium, calcium, or mixed cation channels like AMPA and NMDA receptors) open and allow positive charge to enter, depolarizing the membrane.
Question 5 Short Answer
Why does prolonged or repeated exposure to a neurotransmitter not keep a ligand-gated channel open continuously, even when the neurotransmitter remains bound at the receptor?
Think about your answer, then reveal below.
Model answer: Ligand-gated channels undergo desensitization: after sustained activation, the channel enters a closed, refractory conformation that is distinct from the resting closed state. In the desensitized state, the neurotransmitter may still be bound, but the channel no longer opens. Desensitization is an intrinsic property of the receptor protein — a conformational change that effectively decouples ligand occupancy from gating. It serves as a protective mechanism against overstimulation and shapes the time course of synaptic responses, ensuring that even constant neurotransmitter presence does not produce indefinite ion flow.
Desensitization is distinct from simply having the ligand fall off — it is a separate inactivated state. This is why sustained application of an agonist to a patch of membrane shows an initial peak current that then rapidly declines even with the agonist still present. In synaptic physiology, desensitization helps terminate the postsynaptic response after neurotransmitter release and prevents receptor saturation from causing runaway excitation.