Increased Ca2+ channel currents in cerebellar Purkinje cells of the ataxic groggy rat.
The ataxic groggy rat (strain name; GRY) is an autosomal recessive neurological mutant found in a closed colony of Slc:Wistar rats. Recent genetic analysis has identified the missense (M251K) mutation in the alpha(1) subunit of the Ca(V)2.1 (P/Q-type) voltage-dependent Ca(2+) channel gene (Cacna1a) of GRY rat. In this study, we found that high-voltage-activated (HVA) Ca(2+) channel currents in acutely dissociated Purkinje cells of GRY rats showed increased (not decreased) current density and depolarizing shift of the activation and inactivation curves compared with those of normal Wistar rats. In contrast low-voltage-activated (LVA) Ca(2+) channel currents of GRY rats showed no significant changes. These results suggest that functional alteration of Ca(2+) channel currents in cerebellar Purkinje cells of GRY rats is attributed to the change of HVA Ca(2+) channel currents, and that increased HVA Ca(2+) channel function underlies the cerebellar dysfunction and ataxic phenotype of GRY rats.
Tanaka
Kenta
K
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Shirakawa
Hisashi
H
Okada
Kazuyuki
K
Konno
Masakazu
M
Nakagawa
Takayuki
T
Serikawa
Tadao
T
Kaneko
Shuji
S
D000818:Animals; D000831:Animals, Newborn; D020864:Calcium Channels, N-Type / Q000502:physiology*; D002524:Cerebellar Ataxia / Q000235:genetics / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D020864:Calcium Channels, N-Type