At the GABA-A receptor, benzodiazepines and barbiturates both enhance chloride conductance but differ mechanistically. The correct distinction is:

• A Both act directly on the chloride ion channel independent of GABA binding
• B Benzodiazepines increase the duration of channel opening, barbiturates increase the frequency
• C Both increase only the frequency of channel opening
• D Benzodiazepines increase the frequency of channel opening, barbiturates increase the duration of channel 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 at beta subunit sites and prolong the duration of each opening, and at high concentrations they directly open the channel even without GABA, which explains their lower safety margin and lethality in overdose. Option A describes only barbiturates at toxic concentrations.

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

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