Mg2+ enhances voltage sensor/gate coupling in BK channels
Frank T Horrigan1, Zhongming Ma
1Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. horrigan@mail.med.upenn.edu
The Journal of General Physiology
|January 2, 2008
Summary
Magnesium (Mg2+) and calcium (Ca2+) activate BK (Slo1) potassium channels, but Mg2+ action depends on voltage sensor activation, unlike Ca2+. This reveals distinct allosteric mechanisms for ion channel gating.
Area of Science:
- Molecular biology
- Biophysics
- Ion channel physiology
Background:
- BK (Slo1) potassium channels are crucial for cellular excitability.
- These channels are modulated by intracellular divalent cations like Mg2+ and Ca2+ and membrane voltage.
- Previous studies suggested Mg2+ and Ca2+ act similarly and independently on channel gating.
Purpose of the Study:
- To elucidate the distinct mechanisms by which Mg2+ and Ca2+ modulate BK (Slo1) channel gating.
- To investigate the role of voltage sensor activation in Mg2+ action.
- To understand the allosteric coupling between ion binding and channel opening.
Main Methods:
- Electrophysiological recordings of BK (Slo1) channel activity.
- Measurement of channel open probability (P(O)) and conductance-voltage (G(K)-V) relations.
- Utilized wild-type and mutant (R210C) channels to isolate voltage sensor-dependent effects.
- Analysis of gating currents.
Main Results:
- Mg2+ action on BK (Slo1) channels is dependent on voltage sensor activation, unlike Ca2+.
- Ca2+ increases P(O) even when voltage sensors are in the resting state.
- 10 mM Mg2+ only enhances P(O) when voltage sensors are activated, strengthening allosteric coupling.
- High Mg2+ concentrations (100 mM) show effects more similar to Ca2+.
Conclusions:
- Mg2+ and Ca2+ employ fundamentally different mechanisms to gate BK (Slo1) potassium channels.
- Mg2+ allosterically couples voltage sensor activation to channel opening.
- Understanding these distinct mechanisms is vital for interpreting channel function in physiological contexts.
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