title: Lack of CaV3.1 channels causes severe motor coordination defects and an age-dependent cerebellar atrophy in a genetic model of essential tremor.
abstract: T-type Ca(2+) channels have been implicated in tremorogenesis and motor coordination. The α1 subunit of the Ca(V)3.1 T-type Ca(2+) channel is highly expressed in motor pathways in the brain, but knockout of the Ca(V)3.1 gene (α(1G)(-/-)) per se causes no motor defects in mice. Thus, the role of Ca(V)3.1 channels in motor control remains obscure in vivo. Here, we investigated the effect of the Ca(V)3.1 knockout in the null genetic background of α1 GABA(A) receptor (α1(-/-)) by generating the double mutants (α1(-/-)/α(1G)(-/-)). α1(-/-)/α(1G)(-/-) mice showed severer motor abnormalities than α1(-/-) mice as measured by potentiated tremor activities at 20Hz and impaired motor learning. Propranolol, an anti-ET drug that is known to reduce the pathologic tremor in α1(-/-) mice, was not effective for suppressing the potentiated tremor in α1(-/-)/α(1G)(-/-) mice. In addition, α1(-/-)/α(1G)(-/-) mice showed an age-dependent loss of cerebellar Purkinje neurons. These results suggest that α1(-/-)/α(1G)(-/-) mice are a novel mouse model for a distinct subtype of ET in human and that Ca(V)3.1 T-type Ca(2+) channels play a role in motor coordination under pathological conditions.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Chang
authors.forename: Young-Gyun
authors.initials: YG
authors.lastname: Park
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Park
authors.forename: Gregg E
authors.initials: GE
authors.lastname: Homanics
authors.forename: Jeongjin
authors.initials: J
authors.lastname: Kim
authors.forename: Daesoo
authors.initials: D
authors.lastname: Kim
mesh_terms: D000367:Age Factors; D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology*; D004195:Disease Models, Animal; D020329:Essential Tremor / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009043:Motor Activity / Q000235:genetics; D011689:Purkinje Cells / Q000473:pathology; D011963:Receptors, GABA-A / Q000235:genetics
chemical_list: C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type; D011963:Receptors, GABA-A