Divalent cations selectively alter the voltage dependence of inactivation of A-currents in chick autonomic neurons.

A-currents were studied in acutely dissociated chick autonomic neurons. Switching from salines containing 4 mM Mg2+ to salines containing 4 mM Ca2+ caused a large positive shift in the voltage dependence of steady-state inactivation, but had no effect on the voltage dependence or kinetics of activation, deactivation, the rate at which channels became inactivated, or the rate at which channels recovered from inactivation. This effect saturated with increasing concentrations of Ca2+. Other group IIA divalent cations were less effective than Ca2+, in the order Ca2+ > Ba2+ > Mg2+ = Sr2+. Application of 4 mM Mg2+ partially antagonized the effects of 4 mM Ca2+. The results suggest that divalent cations selectively alter the voltage dependence of steady-state inactivation by acting at sites accessible from the outside of the cell.