Tuning the mechanosensitivity of a BK channel by changing the linker length.
Some large-conductance Ca(2+) and voltage-activated K(+)(BK) channels are activated by membrane stretch. However, the mechanism of mechano-gating of the BK channels is still not well understood. Previous studies have led to the proposal that the linker-gating ring complex functions as a passive spring, transducing the force generated by intracellular Ca(2+) to the gate to open the channel. This raises the question as to whether membrane stretch is also transmitted to the gate of mechanosensitive (MS) BK channels via the linker-gating complex. To study this, we changed the linker length in the stretch-activated BK channel (SAKCaC), and examined the effect of membrane stretch on the gating of the resultant mutant channels. Shortening the linker increased, whereas extending the linker reduced, the channel mechanosensitivity both in the presence and in the absence of intracellular Ca(2+). However, the voltage and Ca(2+) sensitivities were not significantly altered by membrane stretch. Furthermore, the SAKCaC became less sensitive to membrane stretch at relatively high intracellular Ca(2+) concentrations or membrane depolarization. These observations suggest that once the channel is in the open-state conformation, tension on the spring is partially released and membrane stretch is less effective. Our results are consistent with the idea that membrane stretch is transferred to the gate via the linker-gating ring complex of the MS BK channels.
Zhao
Hucheng
H
Institute of Biomechanics and Medical Engineering, Tsinghua University, Beijing 100084, PR China. zhaohc@mail.tsinghua.edu.cn
Sokabe
Masahiro
M
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D007424:Intracellular Fluid / Q000737:chemistry / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008465:Mechanoreceptors / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009154:Mutation / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013347:Subcellular Fractions
D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium