What question did this study set out to answer?

To determine the voltage- and Ca2+-dependent gating mechanisms of large-conductance Ca2+-activated K+ (BK) channels and establish a comprehensive kinetic model.

July 1, 2000The Journal of General PhysiologyOpen Access

Voltage and Ca2+ Activation of Single Large-Conductance Ca2+-Activated K+ Channels Described by a Two-Tiered Allosteric Gating Mechanism

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Population

Cultured rat skeletal muscle (large-conductance Ca2+-activated K+ (BK) channels)

Design

Preclinical

Authors

BRBrad S. RothbergTemple University KMKarl L. MaglebyUniversity of North Carolina at Chapel Hill

Discussion

Member takes

Implication

Offers a comprehensive BK channel gating model; extends allosteric theory but leaves open human translation.

Key Points

To determine the voltage- and Ca2+-dependent gating mechanisms of large-conductance Ca2+-activated K+ (BK) channels and establish a comprehensive kinetic model.
Recorded single-channel currents from cultured rat skeletal muscle BK channels across voltages from -80 to +80 mV and intracellular Ca2+ concentrations from 0.0003 to 1,024 μM.
Measured open probability (Po) limiting slopes, effective gating charge (q_eff), and open and closed dwell-time distributions.
Evaluated kinetic behavior using a 50-state two-tiered allosteric gating model separating voltage-dependent conformational changes from Ca2+-binding steps.
Open probability increased with depolarization with an effective gating charge of 2.3 ± 0.6 e_o (11 mV per e-fold change in Po), remaining largely unchanged across intracellular Ca2+ levels.
Increasing intracellular Ca2+ from 0.03 to 1,024 μM shifted the half-maximal activation voltage (V_1/2) by 175 mV in the hyperpolarizing direction, while V_1/2 was independent of Ca2+ at ≤ 0.03 μM.
A 50-state two-tiered allosteric model successfully reproduced single-channel kinetics over voltages (-80 to +80 mV) and Po (10^-4 to 0.96), showing voltage dependence stems from closed-closed and open-open transitions rather than Ca2+ binding.

Structured PICO

Population

Cultured rat skeletal muscle (large-conductance Ca2+-activated K+ (BK) channels)

Intervention

Varying intracellular Ca2+ concentrations (0.0003 to 1,024 microM) and voltage (+80 to -80 mV)

Outcome

Channel open probability (Po) and single-channel kinetics

The study proposes a 50-state two-tiered allosteric gating mechanism that accurately describes the voltage- and Ca2+-dependent gating of BK channels.

Cite This Study

Rothberg et al. (2000) studied this question.

synapsesocial.com/papers/6a754d1c756843cacbb1f3c8 https://doi.org/10.1085/jgp.116.1.75

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Voltage and Ca2+ Activation of Single Large-Conductance Ca2+-Activated K+ Channels Described by a Two-Tiered Allosteric Gating Mechanism

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Voltage and Ca2+ Activation of Single Large-Conductance Ca2+-Activated K+ Channels Described by a Two-Tiered Allosteric Gating Mechanism

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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