Tuning magnesium sensitivity of BK channels by mutations.

Journal Article (Journal Article)

Intracellular Mg(2+) 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 Mg(2+) binding. In the present study, we show that mutations of E374 or E399 to other amino acids, except for Asp, abolish Mg(2+) sensitivity. These results further support that the side chains of E374 and E399 are essential for Mg(2+) coordination. To the contrary, none of the Q397 mutations abolishes Mg(2+) sensitivity, suggesting that its side chain may not coordinate to Mg(2+). However, because Q397 is spatially close to E374 and E399, its mutations affect the Mg(2+) sensitivity of channel gating by either reducing or increasing the Mg(2+) binding affinity. The pattern of mutational effects and the effect of chemical modification of Q397C indicate that Q397 is involved in the Mg(2+)-dependent activation of BK channels and that mutations of Q397 alter Mg(2+) sensitivity by affecting the conformation of the Mg(2+) binding site as well as by electrostatic interactions with the bound Mg(2+) ion.

Full Text

Duke Authors

Cited Authors

  • Yang, H; Hu, L; Shi, J; Cui, J

Published Date

  • October 15, 2006

Published In

Volume / Issue

  • 91 / 8

Start / End Page

  • 2892 - 2900

PubMed ID

  • 16877509

Pubmed Central ID

  • PMC1578465

International Standard Serial Number (ISSN)

  • 0006-3495

Digital Object Identifier (DOI)

  • 10.1529/biophysj.106.090159


  • eng

Conference Location

  • United States