Zinc blocks the A-type potassium currents in Helix neurons.

The effects of Zn++ on the A-current in neurons of Helix pomatia L. were examined using the current- and voltage-clamp technique. IA was significantly depressed by zinc (Kd = 1.8 mM at -30 mV, nH = 0.6) applied in the perfusate. This depressive effect resulted in a depolarizing shift of the activation curve, associated with reduction of the maximum conductance. Zn++ also caused a depolarizing shift of the steady-state inactivation curve. A dose-response curve for the depolarizing shift of the activation and inactivation curves of IA, as a function of Zn++ concentration, could be fitted by a single binding-site model with an apparent dissociation constant of approximately 1.8 mM. The modulatory action of Zn++ on the A-currents was potential-dependent, being more effective near the resting membrane potential, and decreased with depolarization. In contrast to its effect on IA, zinc caused a slight change in the delayed rectifier K-current but evoked an appreciable attenuation of the leak potassium conductance (Kd = 1.9 mM, nH = 1.1). Zinc suppressed the Ca-currents, too. Addition of zinc caused an increase in the time-to-peak and prolonged the decay time constant of the A-currents in a dose-dependent way (Kd = 1.7 mM, nH = 1.4). In close correlation with the voltage-clamp experiments, Zn++ depolarized the studied neurons, prolonged the action potential duration, suppressed the spike amplitude and increased the firing rate. The results show that Zn++ can evoke a depolarizing shift of both the activation and inactivation fates controlling IA. This modulatory effect of Zn++ on gating of IA appears to reflect binding to a specific, saturable site.