期刊
JOURNAL OF GENERAL PHYSIOLOGY
卷 116, 期 1, 页码 75-99出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.116.1.75
关键词
large-conductance Ca2+-activated K+ channel; K-Ca channel; Monod-Wyman-Changeux; Eigen; Markov
类别
资金
- NIAMS NIH HHS [R01 AR032805, AR32805] Funding Source: Medline
- NINDS NIH HHS [T32 NS007044, NS007044] Funding Source: Medline
The voltage- and Ca2+-dependent grating mechanism of large-conductance Ca2+-activated K+ (BK) channels from cultured rat skeletal muscle was studied using single-channel analysis. Channel open probability (P-o) increased with depolarization, as determined by limiting slope measurements (11 mV per e-fold change in P-o; effective grating charge, q(eff), of 2.3 +/- 0.6 e(o)). Estimates of q(eff) were little changed for intracellular Ca2+ (Ca-i(2+)) ranging from 0.0003 to 1,024 mu M. Increasing Ca-i(2+) from 0.03 to 1,024 mu M shifted the voltage for half maximal activation (V-1/2) 175 mV in the hyperpolarizing direction. V-1/2 was independent of Ca-i(2+) for Ca-i(2+) less than or equal to 0.03 mu M, indicating that the channel can be activated in the absence of Ca-i(2+). Open and closed dwell-time distributions for data obtained at different Ca-i(2+) and voltage, but at the same P-o, were different, indicating that the major action of voltage is not through concentrating Ca2+ at the binding sites. The voltage dependence of P-o arose from a decrease in the mean closing rate with depolarization (q(eff) = -0.5 e(o)) and an increase in the mean opening rate (q(eff) = 1.8 e(o)), consistent with voltage-dependent steps in both the activation and deactivation pathways. A 50-state two-tiered model with separate voltage- and Ca2+-dependent steps was consistent with the major features of the voltage and Ca2+ dependence of the single-channel kinetics over wide ranges of Ca-i(2+) (similar to 0 through 1,024 mu M), voltage (+80 to -80 mV), and P-o (10(-4) to 0.96). In the model, the voltage dependence of the grating arises mainly from voltage-dependent transitions between closed (C-C) and open (O-O) states, with less voltage dependence for transitions between open and closed states (C-O), and with no voltage dependence for Ca2+-binding and unbinding. The two-tiered model can serve as a working hypothesis for the Ca2+- and voltage-dependent gating of the BK channel.
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