Time course of nerve growth factor modulation of ethanol inhibition of Ca2+ currents in PC12 cells

The effects of 25 mM ethanol on high voltage-activated (HVA) L-type Ca2+ channels in nerve growth factor (NGF)-treated, dibutyryl cyclic AMP (dbcAMP)-treated and undifferentiated (UND) PC12 cells were examined. Channels in NGF-treated cells became less sensitive to the effects of ethanol. The time course of the NGF-induced reduction in ethanol inhibition occurred in two phases. The first phase of reduced inhibition was observed after 2 h of NGF exposure and was complete after 5 h. The second phase of reduced inhibition developed over a period of 10-96 h and was reversible after removal of NGF. Exposure to dbcAMP for 2 h also caused a transient drop in ethanol inhibition, but the second phase of decreased ethanol sensitivity was absent. Thus, increased levels of cAMP do not appear to be involved in the longer-term effects of NGF on the decrease in ethanol inhibition of Ca2+ channels, whereas the effects observed at 2 h may involve cAMP.