Ethanol blocks cytosolic Ca super(2+) responses triggered by activation of GABA sub(A) receptor/Cl super(-) channels in cultured proliferating rat neuroepithelial cells

• Published in: Neuroscience Vol. 104; no. 3; pp. 913 - 922
• Main Authors: Ma, W, Pancrazio, J J, Andreadis, J D, Shaffer, K M, Stenger, DA, Li, B-S, Zhang, L, Barker, J L, Maric, D
• Format: Journal Article
• Language: English
• Published: 01-06-2001
• ISSN: 0306-4522

GABA sub(A) receptor/Cl super(-) channels and voltage-gated Ca super(2+) channels are believed to be important sites of ethanol action in the CNS. Acute exposure of ethanol potentiates GABA sub(A) receptor/Cl super(-) channel activity and inhibits voltage-gated Ca super(2+) channels in a number of preparations, mostly post-mitotic neurons. The effects of ethanol on these channels in primary cultures of undifferentiated neural precursor cells remain unknown. To address this issue, we examined the effects of ethanol on GABA sub(A) agonist-activated elevation of cytosolic Ca super(2+) in an in vitro model of the cortical neuroepithelium derived from rat basic fibroblast growth factor-expanded neural precursor cells. We found a potent inhibition of GABA sub(A)-activated elevation of cytosolic Ca super(2+) by ethanol in actively proliferating cells. Since we had recently demonstrated that GABA sub(A) receptor activation depolarizes these cells and elevates their cytosolic Ca super(2+), we tested whether the effects of ethanol involved both GABA sub(A) receptors and voltage-gated Ca super(2+) channels. Both extracellular K super(+)- and muscimol-induced cytosolic Ca super(2+) elevations were abolished by nitrendipine, indicating that both depolarizing stimuli triggered Ca super(2+) influx through L-type voltage-gated Ca super(2+) channels. Exposure of proliferating cells to different concentrations of ethanol revealed that the drug was more potent in blocking muscimol-induced compared to K super(+)-evoked cytosolic Ca super(2+) elevations. These results raise the possibility that ethanol blocks GABAergic stimulation of cytosolic Ca super(2+) levels in proliferating precursors primarily by interacting with GABA sub(A) receptor/Cl super(-) channels and secondarily with voltage-gated Ca super(2+) channels.