Open AccessProtein kinase Cγ in cerebellar Purkinje cells regulates Ca 2+ -activated large-conductance K + channels and motor coordination
Author(s) -
Masashi Watanave,
Nobutaka Takahashi,
Nobutake Hosoi,
Ayumu Konno,
Hikaru Yamamoto,
Hiroyuki Yasui,
Mika Kawachi,
Takuro Horii,
Yasunori Matsuzaki,
Izuho Hatada,
Hirokazu Hirai
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2113336119
Subject(s) - protein kinase c , cerebellum , long term potentiation , climbing fiber , microbiology and biotechnology , knockout mouse , purkinje cell , biology , chemistry , neuroscience , kinase , medicine , biophysics , biochemistry , receptor
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 Ca2+ -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.