A charged residue in S4 regulates coupling among the activation gate, voltage, and Ca2+ sensors in BK channels.
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.
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Related Subject Headings
- Xenopus laevis
- Structure-Activity Relationship
- Static Electricity
- Oocytes
- Neurology & Neurosurgery
- Membrane Potentials
- Large-Conductance Calcium-Activated Potassium Channels
- Ion Channel Gating
- Cells, Cultured
- Calcium
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Xenopus laevis
- Structure-Activity Relationship
- Static Electricity
- Oocytes
- Neurology & Neurosurgery
- Membrane Potentials
- Large-Conductance Calcium-Activated Potassium Channels
- Ion Channel Gating
- Cells, Cultured
- Calcium