Inhibitory effects of amiloride on the current mediated by native GABAA receptors in cultured neurons of rat inferior colliculus

1. The diuretic amiloride is known to modulate the activity of several types of ion channels and membrane receptors in addition to its inhibitory effects on many ion transport systems. However, the effects of amiloride on some important ion channels and receptors, such as GABA_A receptors, in the central nervous system have not been characterized. 2. In the present study, we investigated the functional action of amiloride on native GABA_A receptors in cultured neurons of rat inferior colliculus using whole‐cell patch‐clamp recordings. 3. Amiloride reversibly inhibited the amplitude of the GABA‐induced current (I_GABA) in a concentration‐dependent manner (IC₅₀ 454 ± 24 μmol/L) under conditions of voltage‐clamp with a holding potential at ?60 mV. The inhibition depended on drug application mode and was independent of membrane potential. Amiloride did not change the reversal potential of I_GABA. Moreover, amiloride induced a parallel right‐ward shift in the concentration–response curve for I_GABA without altering the maximal value and Hill coefficient. 4. The present study shows that amiloride competitively inhibits the current mediated by native GABA_A receptors in the brain region, probably via a direct action on GABA‐binding sites on the receptor. The findings suggest that the functional actions of amiloride on GABA_A receptors may result in possible side‐effects on the central nervous system in the case of direct application of this drug into the cerebrospinal fluid for treatment of diseases such as brain tumours.