Inhibition by chloral hydrate and trichloroethanol of AMPA-induced Ca2+ influx in rat cultured cortical neurones

The effects of chloral hydrate and its main metabolite 2,2,2-trichloroethanol were investigated on the (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-induced rise of intracellular Ca2+ concentration ([Ca2+](i)) in cultured non-pyramidal cortical neurones of mts by using single-cell fura-2 microfluorimetry. AMPA elicited a concentration-dependent effect that peaked at 300 mu M (EC50, 7.5 mu M). Responses to AMPA (30 mu M) were markedly inhibited by superfusion with chloral hydrate (IC50, 4.5 mM) or trichloroethanol (IC50, 0.9 mM). By contrast, ethanol (100 mM) caused only slight inhibition. In conclusion, the results demonstrate that chloral hydrate and especially its metabolite trichloroethanol, inhibit the AMPA-induced rise of [Ca2+](i) by depressing the entry of Ca-2 into cortical neurones via the AMPA receptor-channel. (C) 2000 Elsevier Science B.V. All rights reserved.