Functional Coupling of the β(1) Subunit to the Large Conductance Ca(2+)-Activated K(+) Channel in the Absence of Ca(2+) : Increased Ca(2+) Sensitivity from a Ca(2+)-Independent Mechanism

Coexpression of the β(1) subunit with the α subunit (mSlo) of BK channels increases the apparent Ca(2+) sensitivity of the channel. This study investigates whether the mechanism underlying the increased Ca(2+) sensitivity requires Ca(2+), by comparing the gating in 0 Ca(2+) (i) of BK channels composed of α subunits to those composed of α+β(1) subunits. The β(1) subunit increased burst duration ∼20-fold and the duration of gaps between bursts ∼3-fold, giving an ∼10-fold increase in open probability (P (o)) in 0 Ca(2+) (i). The effect of the β(1) subunit on increasing burst duration was little changed over a wide range of P (o) achieved by varying either Ca(2+) (i) or depolarization. The effect of the β(1) subunit on increasing the durations of the gaps between bursts in 0 Ca(2+) (i) was preserved over a range of voltage, but was switched off as Ca(2+) (i) was increased into the activation range. The Ca(2+)-independent, β(1) subunit-induced increase in burst duration accounted for 80% of the leftward shift in the P (o) vs. Ca(2+) (i) curve that reflects the increased Ca(2+) sensitivity induced by the β(1) subunit. The Ca(2+)-dependent effect of the β(1) subunit on the gaps between bursts accounted for the remaining 20% of the leftward shift. Our observation that the major effects of the β(1) subunit are independent of Ca(2+) (i) suggests that the β(1) subunit mainly alters the energy barriers of Ca(2+)-independent transitions. The changes in gating induced by the β(1) subunit differ from those induced by depolarization, as increasing P (o) by depolarization or by the β(1) subunit gave different gating kinetics. The complex gating kinetics for both α and α+β(1) channels in 0 Ca(2+) (i) arise from transitions among two to three open and three to five closed states and are inconsistent with Monod-Wyman-Changeux type models, which predict gating among only one open and one closed state in 0 Ca(2+) (i).