The Journal of General Physiology
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Published 1 November 2001. doi:10.1085/jgp.118.5.589
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© The Rockefeller University Press, 0022-1295/2001//589/ $5.00
Journal of General Physiology, Volume 118, Number 5, 2001

Original Article

Intracellular Mg2+ Enhances the Function of Bk-Type Ca2+-Activated K+ Channels

Jingyi Shia,b and Jianmin Cuia,b

a Cardiac Bioelectricity Research and Training Center, Case Western Reserve University, Cleveland, OH 44106-7207
b Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106-7207
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106-7207.(216) 368-4969

jxc93{at}cwru.edu

BK channels modulate neurotransmitter release due to their activation by voltage and Ca2+. Intracellular Mg2+ also modulates BK channels in multiple ways with opposite effects on channel function. Previous single-channel studies have shown that Mg2+ blocks the pore of BK channels in a voltage-dependent manner. We have confirmed this result by studying macroscopic currents of the mslo1 channel. We find that Mg2+ activates mslo1 BK channels independently of Ca2+ and voltage by preferentially binding to their open conformation. The mslo3 channel, which lacks Ca2+ binding sites in the tail, is not activated by Mg2+. However, coexpression of the mslo1 core and mslo3 tail produces channels with Mg2+ sensitivity similar to mslo1 channels, indicating that Mg2+ sites differ from Ca2+ sites. We discovered that Mg2+ also binds to Ca2+ sites and competitively inhibits Ca2+-dependent activation. Quantitative computation of these effects reveals that the overall effect of Mg2+ under physiological conditions is to enhance BK channel function.

Key Words: magnesium • calcium • BK channel • ion channel gating • competitive inhibition

© 2001 The Rockefeller University Press


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