Protein kinase Cγ in cerebellar Purkinje cells regulates Ca 2+ -activated large-conductance K + channels and motor coordination

Abstract

Significance The cerebellum, the site where protein kinase C (PKC) was discovered, contains the highest amount of PKCγ in the central nervous system. PKCγ in the cerebellum is exclusively confined to Purkinje cells (PCs), sole outputs from the cerebellar cortex. Systemic PKCγ-knockout mice show impaired motor coordination; however, the cause of motor defects remains unknown. Here we show that activation of PKCγ suppresses the Ca 2+ -activated large-conductance K + (BK) channels located along the PC dendrites. A consequential increase in the membrane resistance attenuates electrical signal decay during propagation, resulting in an altered complex spike waveform. Our results suggest that synaptically activated PKCγ in PCs plays a critical role in motor coordination by negative modulation of BK currents.