Mg2+ mediates interaction between the voltage sensor and cytosolic domain to activate BK channels.

Published

Journal Article

The voltage-sensor domain (VSD) of voltage-dependent ion channels and enzymes is critical for cellular responses to membrane potential. The VSD can also be regulated by interaction with intracellular proteins and ligands, but how this occurs is poorly understood. Here, we show that the VSD of the BK-type K(+) channel is regulated by a state-dependent interaction with its own tethered cytosolic domain that depends on both intracellular Mg(2+) and the open state of the channel pore. Mg(2+) bound to the cytosolic RCK1 domain enhances VSD activation by electrostatic interaction with Arg-213 in transmembrane segment S4. Our results demonstrate that a cytosolic domain can come close enough to the VSD to regulate its activity electrostatically, thereby elucidating a mechanism of Mg(2+)-dependent activation in BK channels and suggesting a general pathway by which intracellular factors can modulate the function of voltage-dependent proteins.

Full Text

Duke Authors

Cited Authors

  • Yang, H; Hu, L; Shi, J; Delaloye, K; Horrigan, FT; Cui, J

Published Date

  • November 13, 2007

Published In

Volume / Issue

  • 104 / 46

Start / End Page

  • 18270 - 18275

PubMed ID

  • 17984060

Pubmed Central ID

  • 17984060

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0705873104

Language

  • eng

Conference Location

  • United States