Increased Ca²⁺ channel currents in cerebellar Purkinje cells of the ataxic groggy rat

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• 作者：Kenta Tanaka ; Hisashi Shirakawa ; Kazuyuki Okada ; Masakazu Konno ; Takayuki Nakagawa ; Tadao Serikawa ; Shuji Kaneko
• 关键词：Ataxia ; Mutant rat ; Cerebellar Purkinje cells ; Ca_V2.1 (P/Q-type) Ca²⁺ channel ; Whole-cell patch cl Acutely dissociated preparation
• 刊名：Neuroscience Letters
• 出版年：2007
• 出版时间：16 October 2007
• 年：2007
• 卷：426
• 期：2
• 页码：75-80
• 全文大小：435 K

文摘

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 α₁ subunit of the Ca_V2.1 (P/Q-type) voltage-dependent Ca²⁺ channel gene (Cacna1a) of GRY rat. In this study, we found that high-voltage-activated (HVA) Ca²⁺ 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) Ca²⁺ channel currents of GRY rats showed no significant changes. These results suggest that functional alteration of Ca²⁺ channel currents in cerebellar Purkinje cells of GRY rats is attributed to the change of HVA Ca²⁺ channel currents, and that increased HVA Ca²⁺ channel function underlies the cerebellar dysfunction and ataxic phenotype of GRY rats.