Cloning and functional expression of two families of β-subunits of the large conductance calcium-activated K+ channel

Abstract

We report here a characterization of two families of calcium-activated K+ channel β-subunits, β2 and β3, which are encoded by distinct genes that map to 3q26.2-27. A single β2 family member and four alternatively spliced variants of β3 were investigated. These subunits have predicted molecular masses of 27.1-31.6 kDa, share ~30-44% acid identity with β1, and exhibit distinct but overlapping expression patterns. Coexpression of the β2 or β3a-c subunits with a BK α-subunit altered the functional properties of the current expressed by the α-subunit alone. The β2 subunit rapidly and completely inactivated the current and shifted the voltage dependence for activation to more polarized membrane potentials. In contrast, coexpression of the β3a-c subunits resulted in only partial inactivation of the current, and the β3b subunit conferred an apparent inward rectification. Furthermore, unlike the β1 and β2 subunits, none of the β3 subunits increased channel sensitivity to calcium or voltage. The tissue-specific expression of these β-subunits may allow for the assembly of a large number of distinct BK channels in vivo, contributing to the functional diversity of native BK currents.