Motor deficits in homozygous and heterozygous p/q-type calcium channel mutants.
P/Q-type voltage-dependent Ca(2+) channels (VDCCs) are highly expressed in the cerebellum, and mutations of these channels are associated with disrupted motor function. Several allelic variants of the alpha1A pore-forming subunit of P/Q-type VDCCs have been described, and mice homozygous for these mutations exhibit gait ataxia, as do alpha1A knockout mice. Here we report that heterozygous alpha1A mutants also have a motor phenotype. Mice heterozygous for the leaner and alpha1A knockout mutations exhibit impaired motor learning in the vestibulo-ocular reflex (VOR), suggesting that subtle disruption of P/Q Ca(2+) currents is sufficient to disrupt motor function. Basal VOR and optokinetic reflex performance were normal in the heterozygotes but severely impaired in the leaner and alpha1A knockout homozygotes.
Katoh
Akira
A
Department of Neurobiology, Stanford University, 299 W. Campus Drive, Stanford, CA 94305-5125, USA.
Jindal
Jenelle A
JA
Raymond
Jennifer L
JL
D000818:Animals; D020865:Calcium Channels, P-Type / Q000235:genetics* / Q000502:physiology*; D020907:Calcium Channels, Q-Type / Q000235:genetics* / Q000502:physiology*; D020234:Gait Ataxia / Q000235:genetics* / Q000503:physiopathology*; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009801:Oculomotor Muscles / Q000294:innervation / Q000503:physiopathology; D009802:Oculomotor Nerve / Q000503:physiopathology; D010641:Phenotype; D011597:Psychomotor Performance / Q000502:physiology
D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type