Liu F, Zhang M, Tang ZQ, Lu YG, Chen L
INHIBITORY EFFECTS OF AMILORIDE ON THE CURRENT MEDIATED BY NATIVE GABA RECEPTORS IN CULTURED NEURONS OF RAT INFERIOR COLLICULUS. [JOURNAL ARTICLE]
Clin Exp Pharmacol Physiol 2009 Oct 29.
Summary 1. The diuretic amiloride is known to modulate the activity of several types of ion channels and membrane receptors besides its inhibitory effects on many ion transport systems. In the central nervous system, however, the effects of amiloride on some important ion channels and receptors, such as gamma-aminobutyric acid type A receptors (GABA(A)Rs), are still not characterized. 2. In the present study, we investigated the functional action of amiloride on native GABA(A)Rs in cultured neurons of rat inferior colliculus with whole-cell patch-clamp recordings. 3. Amiloride reversibly inhibited the amplitude of the GABA-induced current (I(GABA)) in a concentration-dependent manner (IC(50) = 454 +/- 23.5 muM) under the condition of voltage-clamp with a holding potential at -60 mV. The inhibition depended on drug application mode and was membrane potential-independent. Amiloride did not change the reversal potential of the I(GABA). Moreover, amiloride shifted the concentration-response curve for the I(GABA) rightward in a parallel manner without altering the maximal value and Hill coefficient. 4. Our study shows that amiloride competitively inhibits the current mediated by native GABA(A)Rs in the brain region, probably through acting directly on the GABA-binding sites on the receptor. Our findings suggest that functional actions of amiloride on GABA(A)Rs 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 tumors.
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