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.