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Original Article

Increased Ca²⁺ Sensitivity from a Ca²⁺-Independent Mechanism

Crina M. Nimigean^a and Karl L. Magleby^a

^a Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33101-6430
Department of Physiology and Biophysics, R430, P.O. Box 016430, Miami, FL 33101-6430.305-243-6898

cnimigea{at}chroma.med.miami.edu

Coexpression of the β₁ subunit with the subunit (mSlo) of BK channels increases the apparent Ca²⁺ sensitivity of the channel. This study investigates whether the mechanism underlying the increased Ca²⁺ sensitivity requires Ca²⁺, by comparing the gating in 0 Ca²⁺_i of BK channels composed of subunits to those composed of +β₁ subunits. The β₁ 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 Ca²⁺_i. The effect of the β₁ subunit on increasing burst duration was little changed over a wide range of P_o achieved by varying either Ca²⁺_i or depolarization. The effect of the β₁ subunit on increasing the durations of the gaps between bursts in 0 Ca²⁺_i was preserved over a range of voltage, but was switched off as Ca²⁺_i was increased into the activation range. The Ca²⁺-independent, β₁ subunit-induced increase in burst duration accounted for 80% of the leftward shift in the P_o vs. Ca²⁺_i curve that reflects the increased Ca²⁺ sensitivity induced by the β₁ subunit. The Ca²⁺-dependent effect of the β₁ subunit on the gaps between bursts accounted for the remaining 20% of the leftward shift. Our observation that the major effects of the β₁ subunit are independent of Ca²⁺_i suggests that the β₁ subunit mainly alters the energy barriers of Ca²⁺-independent transitions. The changes in gating induced by the β₁ subunit differ from those induced by depolarization, as increasing P_o by depolarization or by the β₁ subunit gave different gating kinetics. The complex gating kinetics for both and +β₁ channels in 0 Ca²⁺_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 Ca²⁺_i.

Key Words: maxi-K channel • K_Ca channel • single-channel • mSlo • Monod-Wyman-Changeux

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