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

Huanghe Yang, Lei Hu, Jingyi Shi, Kelli Delaloye, Frank T. Horrigan, Jianmin Cui

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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 Mg2+ and the open state of the channel pore. Mg2+ 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 Mg2+-dependent activation in BK channels and suggesting a general pathway by which intracellular factors can modulate the function of voltage-dependent proteins.

Original languageEnglish
Pages (from-to)18270-18275
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number46
StatePublished - Nov 13 2007


  • Ca -activated K channel
  • Electrostatic interaction
  • Interdomain interaction
  • Magnesium
  • Metal ion regulation


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