BK Channel Modulation by Leucine-Rich Repeat Containing Proteins

Abstract

Molecular diversity of ion channel structure and function underlies variability in electrical signaling in nerve, muscle, and non-excitable cells. Regulation by variable auxiliary subunits is a major mechanism to generate tissue- or cell-specific diversity of ion channel function.Mammalian large-conductance, voltage and calcium-activated potassium (BK, KCa1.1) channels are ubiquitously expressed with diverse functions in different tissues or cell types, consisting of the pore-forming, voltage- and Ca2+-sensing α-subunits (BKα), or together with the tissue-specific auxiliary subunits, previously known as four β-subunits (β1 - β4). We previously identified a leucine-rich repeat (LRR) containing protein, LRRC26, as a new type of BK channel auxiliary subunit, which causes an unprecedented large negative shift in voltage dependence of channel activation. Here we report a group of LRRC26 paralogous proteins LRRC52, LRRC55 and LRRC38 that potentially function as LRRC26-type auxiliary subunits of BK channels. LRRC52, LRRC55 and LRRC38 produce marked shifts in the BK channel's voltage dependence of activation in hyperpolarization direction to different extents. They together with LRRC26 show distinct expression in different human tissues and may have a broad influence of the BK channel function in different tissues or cell types.