BK Channel Gamma3 Subunit (LRRC55) Knock-Out Mice Show Ataxia-Like Phenotype

Abstract

The large-conductance, calcium- and voltage-activated K+ (BK) channel consists of the pore-forming α subunits (BKα) and the tissue-specific auxiliary subunits. The auxiliary γ3 subunits (LRRC55) modulate the BK channel by shifting the voltage-dependence of channel activation toward the hyperpolarizing direction by approximately 50 mV in the absence of calcium. Previous study showed that LRRC55 is expressed mainly in brains. In this study, we generated LRRC55 knock-out mice and investigated the LRRC55 expression and function in mouse brains. We found that LRRC55 is abundantly expressed in the cerebellum Purkinje cells. LRRC55 knock-out mice performed normally in open-field test, but showed gait abnormality in footprint test. Therefore, deficiency of LRRC55 leads to an ataxia-like phenotype in mice. Our findings suggest an important role of LRRC55 in BK channel regulation in cerebellum.