Ethanol blocks cytosolic Ca2+ responses triggered by activation of GABA(A)receptor/Cl- channels in cultured proliferating rat neuroepithelial cells

GABA(A) receptor/Cl- channels and voltage-gated Ca2+ channels are believed to be important sites of ethanol action in the CNS. Acute exposure of ethan ol potentiates GABAA receptor/Cl- channel activity and inhibits voltage-gat ed Ca2+ channels in a number of preparations. mostly post-mitotic neurons. The effects of ethanol on these channels in primary cultures of undifferent iated neural precursor cells remain unknown. To address this issue, wr exam ined the effects of ethanol on GABAA agonist-activated elevation of cytosol ic Ca2+ in an in vitro model of the cortical neuroepithelium derived from r at basic fibroblast growth factor-expanded neural precursor cells. We found a potent inhibition of GABA(A)-activated elevation of cytosolic Ca2+ by et hanol in actively proliferating cells. Since we had recently demonstrated t hat GABAA receptor activation depolarizes these cells and elevates their cy tosolic Ca2+, we tested whether the effects of ethanol involved both GABAA receptors and voltage-gated Ca'' channels. Both extracellular K-- and musci mol-induced cytosolic Ca2+ elevations were abolished by nitrendipine, indic ating that both depolarizing stimuli triggered Ca2+ influx through L-type v oltage-gated Ca2+ channels. Exposure of proliferating cells to different co ncentrations of ethanol revealed that the drug was more potent in blocking muscimol-induced compared to K+-evoked cytosolic Ca2+ elevations. These results raise the possibility that ethanol blocks GABAergic stimulati on of cytosolic Ca2+ levels in proliferating precursors primarily by intera cting with GABA(A) receptoriC1 channels and secondarily with voltage-gated Ca2+ channels. Published by Elsevier Science Ltd on behalf of IBRO.