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. (C) 1994 Elsevier Science Inc. All rights reserved.