GABA-A channel physiology — MRCPsych Paper A MCQ

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EasyNeurophysiology and neurochemistryGABA-A channel physiologyMRCPsych Paper A

A 49-year-old man becomes drowsy after receiving lorazepam for severe agitation. Lorazepam enhances inhibitory signalling through GABA-A receptors. Which change in ion-channel gating is classically associated with benzodiazepines?

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Correct answer: C — Increased frequency of chloride channel opening

Lorazepam is a benzodiazepine and a positive allosteric modulator of the GABA-A receptor, a ligand-gated chloride channel. Benzodiazepines enhance the effect of GABA and are classically described as increasing the frequency of chloride-channel opening, producing neuronal hyperpolarisation and sedation. Therefore, C is correct. Increased chloride-channel open duration is the traditional contrasting mechanism associated with barbiturates, making B the principal distractor. Voltage-gated sodium-channel blockade is associated with drugs such as local anaesthetics and several antiseizure medicines. Inhibition of vesicular dopamine storage describes VMAT inhibition, as with reserpine or tetrabenazine. Tyrosine kinase activation is a mechanism of enzyme-linked receptors, not GABA-A receptors.

Reference: Bianchi MT, Botzolakis EJ, Lagrange AH, Macdonald RL. Benzodiazepine modulation of GABA(A) receptor opening frequency depends on activation context: a patch clamp and simulation study. Epilepsy Research. 2009;85:212–220. https://pubmed.ncbi.nlm.nih.gov/19447010/