Both benzodiazepines and barbiturates potentiate GABA-A receptor mediated inhibition, but they differ in how they modify the chloride channel. The correct distinction is:

• A Benzodiazepines prolong the duration of each chloride channel opening, barbiturates increase the frequency of openings
• B Barbiturates require endogenous GABA to be present, benzodiazepines do not
• C Both drugs act solely by increasing the frequency of channel openings
• D Benzodiazepines increase the frequency of chloride channel openings, barbiturates prolong their open duration ✓

Explanation

Benzodiazepines bind at the interface of the alpha and gamma subunits and enhance GABA binding, increasing the frequency of chloride channel openings. Barbiturates prolong the open duration of each channel and, unlike benzodiazepines, can open the channel directly at high concentrations even without GABA, which explains their lower safety margin. Option B reverses this GABA-dependence relationship and is therefore wrong.

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

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