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.
Noh
Jihyun
J
Department of Brain & Cognitive Sciences and Division of Life & Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
Kim
Min-Kyung
MK
Chung
Jun-Mo
JM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000502:physiology*; D002413:Cations, Divalent; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000166:cytology / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology / Q000502:physiology*
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002413:Cations, Divalent; D015032:Zinc