To elucidate biophysical mechanisms underlying the Zn2+ block on the low-threshold T-type Ca2+ current (IT), we examined the Zn2+-induced alterations of gating properties of IT of a rat thalamic relay neuron and of α1G 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 IT. Except for the inactivation near the activation threshold of IT, 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 α1G channel was almost insensitive to Zn2+. All these results imply that Zn2+ alters the gating properties of IT mainly by accelerating its deactivation process.
Bibliographical noteFunding Information:
We gratefully acknowledge Dr. Jeong SW (Yonsei Univ., Korea) for kindly supplying α1G-transfected HEK-293 cells. This work was supported by Systems Biology Research Program from GIST and Special Research Grant from EWU to JMC. Noh: BK21 scholarship recipient.
- Channel blocker
- Gating kinetics
- Metal ion
- Voltage-gated calcium channel