Title : BK potassium channel modulation by leucine leucine-rich repeat-containing proteins
Abstract :
Molecular diversity of ion channel structure and function underlies variability in electrical signaling in nerve, muscle, and nonexcitable 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 channels (BK, K( Ca)1 .1) are ubiquitously expressed with diverse functions in different tissues or cell types, consisting of the pore-forming, voltage- and Ca(2 +)-sensing α-subunits ( BKα) , either alone or together with the tissue-specific auxiliary β-subunits (β1-β4)
We recently identified a leucine-rich repeat (LRR)-containing membrane protein leucine-rich repeat (LRR)-containing membrane protein, LRRC26 , as a BK channel auxiliary subunit , which causes an unprecedented large negative shift (∼140 mV) 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 a marked shift in the BK channel 's voltage dependence of activation in the hyperpolarizing direction by ∼100 mV, 50 mV, and 20 mV, respectively, in the absence of calcium
They along with LRRC26 show distinct expression in different human tissues: LRRC26 and LRRC38 mainly in secretory glands, LRRC52 in testis, and LRRC55 in brain
LRRC26 and its paralogs are structurally and functionally distinct from the β-subunits and we designate them as a γ family of the BK channel auxiliary proteins , which potentially regulate the channel's gating properties over a spectrum of different tissues or cell types