British journal of pharmacology
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The modulation of the gamma-aminobutyric acidA (GABAA) receptor by alphaxalone has been investigated by use of voltage-clamp recordings from enzymatically isolated bovine chromaffin cells maintained in cell culture. Alphaxalone (greater than 30 nM) reversibly and dose-dependently potentiated the amplitude of membrane currents elicited by locally applied GABA (100 microM). The potentiation was not associated with a change in the reversal potential of GABA-evoked currents and was not influenced by the benzodiazepine receptor antagonist, Ro15-1788 (300 nM). ⋯ The beta-hydroxy isomer of alphaxalone, betaxalone (100 nM-1 microM), did not potentiate GABA-induced currents, nor did higher concentrations of the steroid (10-100 microM) directly evoke a membrane current. However, over the latter concentration range, betaxalone suppressed the amplitude of currents elicited either by GABA or ACh. The relevance of the present results to the anaesthetic action of alphaxalone is discussed together with the broader implications of steroidal modulation of the GABAA receptor.