Resistance to tremor and aAbnormal motor gating in mice lacking α1G- T-type calcium channel

Abstract

Low voltage-activated (LVA) T-type $Ca^{2+}$ channels play a crucial role in the control of cellular excitability under diverse physiological and pathological processes. Here, by using mice lacking α1G T-type $Ca^{2+}$ channels, their roles in the motor-associated mechanisms are tried to be characterized. Since α1G mutant mice $(α1G^{+/-}, α1G^{-/-})$ showed no significant motor defects, behavioral tests were performed in different pharmacological and genetic conditions. In response to harmaline, a tremorogenic drug, α1G mutant mice $(α1G^{+/-}, α1G^{-/-})$ exhibited a reduced tremor, as measured by shorter duration and smaller amplitude of tremor when compared with wild-type mice $(α1G^{+/+})$ although the frequency of tremor were not significantly different between genotypes. Consistently, in open-field test, the α1G-/- mice were relatively resistant to the harmaline-induced motor inhibition since they showed higher locomotor activities than wild-type mice. In addition, in α1A hetero-genetic background, double mutant mice $(α1G^{-/-} ; α1A^{+/-})$ exhibited severe ataxia and sporadic dystonia. The present results first provide an in vivo evidence for the contribution of T-type $Ca^{2+}$ channels to motor function and suggest that the modulation of T-type $Ca^{2+}$ channels could be a relevant therapeutic strategy for helping patient with motor abnormalities.