A charged residue in S4 regulates coupling among the activation gate, voltage, and Ca2+ sensors in BK channels.

Published

Journal Article

Coupling between the activation gate and sensors of physiological stimuli during ion channel activation is an important, but not well-understood, molecular process. One difficulty in studying sensor-gate coupling is to distinguish whether a structural perturbation alters the function of the sensor, the gate, or their coupling. BK channels are activated by membrane voltage and intracellular Ca(2+) via allosteric mechanisms with coupling among the activation gate and sensors quantitatively defined, providing an excellent model system for studying sensor-gate coupling. By studying BK channels expressed in Xenopus oocytes, here we show that mutation E219R in S4 alters channel function by two independent mechanisms: one is to change voltage sensor activation, shifting voltage dependence, and increase valence of gating charge movements; the other is to regulate coupling among the activation gate, voltage sensor, and Ca(2+) binding via electrostatic interactions with E321/E324 located in the cytosolic side of S6 in a neighboring subunit, resulting in a shift of the voltage dependence of channel opening and increased Ca(2+) sensitivity. These results suggest a structural arrangement of the inner pore of BK channels differing from that in other voltage gated channels.

Full Text

Duke Authors

Cited Authors

  • Zhang, G; Yang, H; Liang, H; Yang, J; Shi, J; McFarland, K; Chen, Y; Cui, J

Published Date

  • September 10, 2014

Published In

Volume / Issue

  • 34 / 37

Start / End Page

  • 12280 - 12288

PubMed ID

  • 25209270

Pubmed Central ID

  • 25209270

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.1174-14.2014

Language

  • eng

Conference Location

  • United States