Redox-sensitive extracellular gates formed by auxiliary β subunits of calcium-activated potassium channels

An important step to understanding ion channels is identifying the structural components that act as the gates to ion movement. Here we describe a new channel gating mechanism, produced by the β3 auxiliary subunits of Ca²⁺-activated, large-conductance BK-type K⁺ channels when expressed with their pore-forming α subunits. BK β subunits have a cysteine-rich extracellular segment connecting two transmembrane segments, with small cytosolic N and C termini. The extracellular segments of the β3 subunits form gates to block ion permeation, providing a mechanism by which current can be rapidly diminished upon cellular repolarization. Furthermore, this gating mechanism is abolished by reduction of extracellular disulfide linkages, suggesting that endogenous mechanisms may regulate this gating behavior. The results indicate that auxiliary β subunits of BK channels reside sufficiently close to the ion permeation pathway defined by the α subunits to influence or block access of small molecules to the permeation pathway.