A novel mechanism of zinc block on α1G-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 Zn2+-induced alterations of gating properties of I-T of a rat thalamic relay neuron and of alpha 1G 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 alpha 1G 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. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.