Divalent cation modulation of a-type potassium channels in acutely dissociated central neurons from wide-type and mutant Drosophila.

Drosophila mutants provide an ideal model to study channel-type specificity of ion channel regulation in situ. In this study, the effects of divalent cations on voltage-gated K+ currents were investigated in acutely dissociated central neurons of Drosophila third instar larvae using the whole-cell patch-clamp recording. Our data showed that micromolar Cd2+ enhanced the peak inactivating current (I(A)) without affecting the delayed component (I(K)). The same results were obtained in Ca(2+)-free external solution, and from slo1 mutation, which eliminates transient Ca(2+)-activated K+ current. Micromolar Cd2+ and Zn2+, and millimolar Ca2+ and Mg2+ all shifted the steady-state inactivation curve of I(A) without affecting the voltage-dependence of I(A) activation, whereas millimolar Cd2+ markedly affected both the activation and steady-state inactivation curves for I(A). Divalent cations affected I(A) with different potency; the sequence was: Zn2+ > Cd2+ > Ca2+ > Mg2+. The modulation of I(A) by Cd2+ was partially inhibited in Sh(M), a null Shaker (one of I(A)-encoding genes) mutation. Taken together, the channel-type specificity, the asymmetric effects on I(A) activation and inactivation kinetics, and the diverse potency of divalent cations all strongly support the idea that physiological divalent cations modulate A-type K+ channels through specific binding to extracellular sites of the channels.