A Charged Residue in S4 Regulates Coupling among the Activation Gate, Voltage, and Ca super(2+) Sensors in BK Channels

• Published in: The Journal of neuroscience Vol. 34; no. 37; pp. 12280 - 12288
• Main Authors: Zhang, Guohui, Yang, Huanghe, Liang, Hongwu, Yang, Junqiu, Shi, Jingyi, McFarland, Kelli, Chen, Yihan, Cui, Jianmin
• Format: Journal Article
• Language: English
• Published: 10.09.2014
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1174-14.2014

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 super(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 super(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 super(2+) sensitivity. These results suggest a structural arrangement of the inner pore of BK channels differing from that in other voltage gated channels.