Both barbiturates and benzodiazepines facilitate GABAergic transmission at the GABA-A receptor, yet their electrophysiological effects differ. The distinction is:

• A Barbiturates increase the frequency of chloride channel opening, benzodiazepines increase its duration
• B Both act exclusively by increasing the frequency of channel opening
• C Barbiturates increase the duration of chloride channel opening, benzodiazepines increase its frequency ✓
• D Barbiturates block the chloride channel, benzodiazepines prolong its opening

Explanation

Benzodiazepines bind at the interface of the alpha and gamma subunits and increase the frequency of GABA-gated chloride channel openings. Barbiturates bind a separate site on the beta subunit and prolong the duration of each opening, and at high concentrations can open the channel directly without GABA, which explains their lower safety margin and respiratory depression in overdose.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

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