Effects of multiple metal binding sites on calcium and magnesium-dependent activation of BK channels.

Published

Journal Article

BK channels are activated by physiological concentrations of intracellular Ca2+ and Mg2+ in a variety of cells. Previous studies have identified two sites important for high-affinity Ca2+ sensing between [Ca2+]i of 0.1-100 microM and a site important for Mg2+ sensing between [Mg2+]i of 0.1-10 mM. BK channels can be also activated by Ca2+ and Mg2+ at concentrations>10 mM so that the steady-state conductance and voltage (G-V) relation continuously shifts to more negative voltage ranges when [Mg2+]i increases from 0.1-100 mM. We demonstrate that a novel site is responsible for metal sensing at concentrations>=10 mM, and all four sites affect channel activation independently. As a result, the contributions of these sites to channel activation are complex, depending on the combination of Ca2+ and Mg2+ concentrations. Here we examined the effects of each of these sites on Ca2+ and Mg2+-dependent activation and the data are consistent with the suggestion that these sites are responsible for metal binding. We provide an allosteric model for quantitative estimation of the contributions that each of these putative binding sites makes to channel activation at any [Ca2+]i and [Mg2+]i.

Full Text

Duke Authors

Cited Authors

  • Hu, L; Yang, H; Shi, J; Cui, J

Published Date

  • January 2006

Published In

Volume / Issue

  • 127 / 1

Start / End Page

  • 35 - 49

PubMed ID

  • 16344323

Pubmed Central ID

  • 16344323

International Standard Serial Number (ISSN)

  • 0022-1295

Digital Object Identifier (DOI)

  • 10.1085/jgp.200509317

Language

  • eng

Conference Location

  • United States