Effect of ethanol on calcium regulation in rat fetal hypothalamic cells in culture.
The effects of acute exposure to ethanol on calcium regulation in primary cultures of rat fetal hypothalamic cells was studied with the use of the calcium indicator fura-2 and digital imaging techniques. We found that ethanol caused cytoplasmic calcium to increase in a dose-dependent and reversible manner, and these increases could be observed at pharmacologically relevant doses (34 mM). At 170 mM ethanol 65% of 1059 cells examined responded to ethanol with an increase in cytoplasmic calcium. Removing bath calcium eliminated the ethanol-induced calcium response in most cells (76% of 427 cells). In most cells exposure to thapsigargin (20 nM) had no significant effect on the ethanol-induced calcium increase (87% of 67 cells examined). The ethanol-induced calcium increase was reduced by 79+/-5% (n=110 cells) by the P/Q-type calcium channel blocker omega-agatoxin-TK (20 nM), by 51+/-10% (n=115 cells) by the N-type calcium channel blocker omega-conotoxin-GVIA (100 nM), and by 26+/-3% (n=90 cells) by the T-type calcium channel blocker flunarizine (1 microM). The L-type calcium channel blocker nifedipine (1 microM) had complex actions, sometimes inhibiting and sometimes increasing the calcium response. These results demonstrate that ethanol can directly modulate cytoplasmic calcium levels in hypothalamic cells mostly by a pathway that involves extracellular calcium and voltage-dependent calcium channels, and that this response may participate in the biological effects of acute ethanol exposure.
Simasko
S M
SM
Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, College of Veterinary Medicine, 205 Wegner Hall, Washington State University, Pullman, WA 99164-6520, USA.simasko@vetmed.wsu.ed
Boyadjieva
N
N
De
A
A
Sarkar
D K
DK
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D051381:Rats / Q000196:embryology
D002121:Calcium Channel Blockers; D000431:Ethanol; D002118:Calcium