Mg2+ mediates interaction between the voltage sensor and cytosolic domain to activate BK channels.
Journal Article (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
- PMC2084332
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.0705873104
Language
- eng
Conference Location
- United States