Ethacrynic acid: effects on postsynaptic GABA responses and electric activity of CA3 neurones

Ethacrynic acid (ETA) inhibits somatic Cl(-)-extrusion from hippocampal pyramidal neurones. We analysed the dependence of postsynaptic gamma-aminobutyric acid (GABA) responses on this Cl- extrusion. ETA irreversibly reduced the 'somatic' hyperpolarizing GABAA response (hGABAA) within a few minutes, without altering the following depolarizing GABAA (dGABAA) and hyperpolarizing GABAB responses. GABA-induced changes of the membrane resistance were not affected by ETA, indicating that ETA does not act primarily on receptor-operated channels. In about 50% of the tested CA3 neurones spontaneous activity and caffeine-induced epileptiform discharges increased initially after adding ETA. All neurones lost their activity during prolonged ETA exposure. The early ETA-induced increase of neuronal activity coincided with the decrease of hGABAA (disinhibition). The late suppressive action may be caused by intracellular acidosis.