Inhibitory effects of amiloride on the current mediated by native GABA(A) 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 (IC(50) 454 +/- 24 micromol/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.
Liu
Feng
F
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.
Zhang
Min
M
Tang
Zhen-Quan
ZQ
Lu
Yun-Gang
YG
Chen
Lin
L
D000584:Amiloride / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004232:Diuretics / Q000009:adverse effects / Q000494:pharmacology*; D018756:GABA Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D007245:Inferior Colliculi / Q000166:cytology / Q000187:drug effects*; D007700:Kinetics; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology; D055366:Synaptic Potentials / Q000187:drug effects*
D004232:Diuretics; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D026941:Sodium Channel Blockers; D000584:Amiloride