Two classes of regulatory subunits coassemble in the same BK channel and independently regulate gating

TL;DR

This study shows that two types of regulatory proteins can coexist in the same BK channel and independently influence its function.

Contribution

The study reveals that β and γ subunits can coassemble in BK channels and independently regulate their gating.

Findings

γ1 and up to four β2 subunits can coexist in the same BK complex.

The functional effects of β2 subunits are largely additive with those of γ1 subunits.

Different β:γ stoichiometries produce BK channels with distinct functional properties.

Abstract

High resolution proteomics increasingly reveals that most native ion channels are assembled in macromolecular complexes. However, whether different partners have additive or cooperative functional effects, or whether some combinations of proteins may preclude assembly of others are largely unexplored topics. The large conductance Ca2+-and-voltage activated potassium channel (BK) is well-suited to discern nuanced differences in regulation arising from combinations of subunits. Here, we examine whether assembly of two different classes of regulatory proteins, β and γ, in BK channels is exclusive or independent. Our results show that both γ1 and up to four β2 subunits can coexist in the same functional BK complex, with the gating shift caused by β2 subunits largely additive with that produced by the γ1 subunit(s). The multiplicity of β:γ combinations that can participate in a BK complex therefore allow a range of BK channels with distinct functional properties tuned by the specific stoichiometry of the contributing subunits.

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