Double effect of ethanol on intracellular Ca2+ levels in undifferentiated PC12 cells

In PC12, a cellular line derived from a rat pheochromocytoma, ethanol (EtOH) induces a different effect depending on the concentration used. When resting cells are incubated with an alcohol concentration less than or equal to 120 mM, the [Ca2+]i increased with a double phase pattern. If the alcohol concentration was increased over 120-160 mM, EtOH reversed its effect and the [Ca2+]i decreased. This decrease was strongly inhibited if KCl-depolarized cells were used and was completely abolished if the substrate constituted EtOH-chronically treated cells. The Ca2+ increase is the consequence of an activation of L-type voltage-activated channels, while the other voltage-dependent channels (N-type), the receptor-operated channels and the Ca2+ extrusion pump present in these cells are not involved in EtOH action. These findings indicate that EtOH can induce (by different mechanisms) both potentiating and inhibiting effects on [Ca2+]i in PC12 cells in relation to the alcohol dose effectively present in the suspension medium.