Methanol elevates cytosolic calcium ions in cultured canine cerebral vascular smooth muscle cells: possible relation to CNS toxicity.
Acute exposure of cultured canine cerebral vascular smooth muscle cells to methanol (10-400 mM) results in concentration-dependent elevation of the concentration of intracellular free calcium ion ([Ca2+]i) as measured with the fluorescent indicator, fura-2, and digital imaging microscopy. The resting level of [Ca2+]i in the cerebral vascular smooth muscle cells was 89.3+/-5.3 nM. Exposure of these cells to 10 mM methanol for only 5 min resulted in significant elevation in [Ca2+]i (i.e., to 105.7+/-4.6) (p < 0.05). Methanol (10 mM) is a concentration found in the blood of victims demonstrating early CNS toxicity. Other, higher concentrations of methanol rapidly raised [Ca2+]i upwards of 60% over basal resting levels. These result suggest that methanol-induced cerebral vasospasm is a consequence of large rises in intracellular Ca2+. These events could play a crucial role in methanol-induced cerebral edema, brain hemorrhage, and cerebral and retinal infarcts, eventuating in severe deficits in brain blood flow and the known, subsequent CNS disturbances.
Li
W
W
Department of Physiology, State University of New York, Health Science Center at Brooklyn, 11203, USA.
Zheng
T
T
Wang
J
J
Altura
B T
BT
Altura
B M
BM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects*; D004285:Dogs; D002546:Ischemic Attack, Transient / Q000209:etiology; D008297:Male; D000432:Methanol / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D012997:Solvents / Q000494:pharmacology*
D012997:Solvents; D002118:Calcium; D000432:Methanol