Ethanol-induced increases in [Ca²⁺]_i and inositol (1,4,5) triphosphate in rat hepatocytes

Rat hepatocytes were studied for [Ca²⁺]_i with Fura-2 at the single cell level using a microfluorometer-imaging system which showed that both the number of cells elevating [Ca²⁺]_i and the magnitude of [Ca²⁺]_i increase were directly dependent upon ethanol concentration between 50 mM and 1 M. Peak [Ca²⁺]_i increases ranged from 27 nM with 50 mM ethanol to 57 nM after 1 M ethanol. Ethanol appeared to initiate calcium release from intracellular stores and caused a dose dependent production of inositol(1,4,5) triphosphate (Ins(1,4,5)P₃) in hepatocytes. Low concentrations of ethanol (50 - 100 mM) did not significantly raise Ins(1,4,5)P₃ although 300 mM - 1 M increased Ins(1,4,5)P₃ comparable to that found with vasopressin (5 nM). In summary, physiologic amounts of ethanol raise [Ca²⁺]_i in rat hepatocytes, although at lower levels (50 - 100 mM) the changes may or may not be related to an Ins(1,4,5)P₃ pathway.