A novel mechanism of zinc block on alpha1G-like low-threshold T-type Ca2+ channels in a rat thalamic relay neuron.

To elucidate biophysical mechanisms underlying the Zn2+ block on the low-threshold T-type Ca2+ current (I(T)), we examined the Zn(2+)-induced alterations of gating properties of I(T) of a rat thalamic relay neuron and of alpha1G channels expressed in HEK-293 cells, using a whole-cell voltage clamp technique. The effect of Zn2+ block depended upon holding potentials but not test potentials, indicating that, the greater the inactivation, the less Zn2+ blocked I(T). Except for the inactivation near the activation threshold of I(T), no significant changes in the kinetics of activation and inactivation were induced by Zn2+. In contrast, the rates of both de-inactivation and deactivation were dramatically increased by Zn2+, and moreover the channels were rapidly re-blocked upon re-polarization under Zn2+. Furthermore, the outward current via alpha1G channel was almost insensitive to Zn2+. All these results imply that Zn2+ alters the gating properties of I(T) mainly by accelerating its deactivation process.