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

We report here a characterization of two families of calcium-activated K+ channel beta-subunits, beta 2 and beta 3, which are encoded by distinct genes that map to 3q26.227, A single beta 2 family member and four alternatively spliced variants of beta 3 were investigated. These subunits have predicted molecular masses of 27.1-31.6 kDa, share similar to 30-44% amino acid identity with beta 1, and exhibit distinct but overlapping expression patterns. Coexpression of the beta 2 or beta 3a-c subunits with a BK alpha-subunit altered the functional properties of the current expressed by the alpha-subunit alone. The beta 2 subunit rapidly and completely inactivated the current and shifted the voltage dependence for activation to more polarized membrane potentials. In contrast, coexpression of the beta 5a-c subunits resulted in only partial inactivation of the current, and the beta 3b subunit conferred an apparent inward rectification. Furthermore, unlike the beta 1 and beta 2 subunits, none of the beta 3 subunits increased channel sensitivity to calcium or voltage. The tissue-specific expression of these beta-subunits may allow for the assembly of a large number of distinct BK channels in vivo, contributing to the functional diversity of native BR currents.