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.
Bonnet
U
U
Rheinische Landes- und Hochschulklinik für Psychiatrie, Essen, Germany.
Gastpar
M
M
Bingmann
D
D
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004594:Electrophysiology; D004976:Ethacrynic Acid / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018079:Receptors, GABA / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*
D000697:Central Nervous System Stimulants; D018118:Chloride Channels; D004232:Diuretics; D018079:Receptors, GABA; D002110:Caffeine; D004976:Ethacrynic Acid