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 α1 subunit of the CaV2.1 (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.