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Biophys. J. BioFAST: First Published July 28, 2006. doi:10.1529/biophysj.106.090159
© 2006 by the Biophysical Society.

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CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING

Tuning Magnesium Sensitivity of BK Channels by Mutations

Huanghe Yang 1, Lei Hu 1, Jingyi Shi 1 and Jianmin Cui 2*

1 Washington Univeristy
2 Washington University

* To whom correspondence should be addressed. E-mail: jcui{at}biomed.wustl.edu.

Submitted on May 30, 2006
Revised on June 27, 2006
Accepted on 18 July 2006


  Abstract
Intracellular Mg2+ at physiological concentrations activates mSlo1 BK channels by binding to a metal binding site in the cytosolic domain. Previous studies suggest that residues E374, Q397 and E399 are important in Mg2+ binding. In the present study, we show that mutations of E374 or E399 to other amino acids, except for Asp, abolish Mg2+ sensitivity. These results further support that the side-chains of E374 and E399 are ligands for the Mg2+ binding site and demonstrate that the caboxylates on these two residues are essential for Mg2+ coordination. To the contrary, none of the Q397 mutations abolish Mg2+ sensitivity, suggesting that its side-chain may not coordinate to Mg2+. However, since Q397 is spatially close to E374 and E399, its mutations affect the Mg2+ sensitivity of channel gating by either reducing or increasing the Mg2+ binding affinity. The pattern of mutational effects and the effect of chemical modification of Q397C indicate that Q397 is involved in the Mg2+-dependent activation of BK channels and the mutations of Q397 alter Mg2+ sensitivity by affecting the conformation of the Mg2+ binding site as well as by electrostatic interactions with the bound Mg2+ ion.

Key Words: BK channel, Chemical Modification, Ion channel gating, Magnesium, Mutation




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Copyright © 2006 by the Biophysical Society.