LINGO1 is a regulatory subunit of large conductance, Ca <sup>2+</sup> -activated potassium channels
Srikanth Dudem, Roddy J. Large, Shruti G. Kulkarni, Heather McClafferty, Irina G. Tikhonova, Gerard P. Sergeant, K. D. Thornbury, Michael J. Shipston, Brian A. Perrino, Mark A. Hollywood
Abstract
Significance Large conductance calcium-activated potassium (BK) channels are ubiquitously expressed and alter cellular excitability. These channels are formed by four pore-forming α subunits whose biophysical and pharmacological properties are modulated by regulatory β and γ subunits. LINGO1 is a protein, previously shown to be upregulated in both Parkinson’s disease and Essential Tremor. Consequently, we investigated its effects on BK channels and demonstrate that LINGO1 associates with these channels in human cerebellum. LINGO1 causes BK channels to inactivate and to open at more negative potentials. Furthermore, coexpression of BK with LINGO1 also led to a reduction in BK channels in the membrane. Our data support the idea that LINGO1 is a regulatory subunit of BK channels.