Barbiturates such as thiopentone and benzodiazepines both act at the GABA-A receptor complex, yet their electrophysiological effects differ. How does a barbiturate modify chloride channel behaviour compared with a benzodiazepine?

• A It prolongs the duration of channel opening, unlike benzodiazepines which increase frequency of opening ✓
• B It increases the frequency of channel opening, unlike benzodiazepines which prolong open duration
• C It directly opens the chloride channel independently of GABA, unlike benzodiazepines which require GABA
• D It blocks the chloride channel, producing excitation at high concentrations

Explanation

Barbiturates bind a site distinct from the benzodiazepine site and prolong the duration of GABA-gated chloride channel opening, increasing current flow per opening. Benzodiazepines instead increase the frequency of channel opening. At very high anaesthetic concentrations barbiturates can open the channel without GABA, explaining their ability to induce burst suppression, an effect benzodiazepines cannot achieve. Option D describes a convulsant action barbiturates do not possess.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

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