Membrane stretch and cytoplasmic Ca2+ independently modulate stretch-activated BK channel activity.
Large conductance Ca(2+)-activated K(+) (BK) channels are responsible for changes in chemical and physical signals such as Ca(2+), Mg(2+) and membrane potentials. Previously, we reported that a BK channel cloned from chick heart (SAKCaC) is activated by membrane stretch. Molecular cloning and subsequent functional characterization of SAKCaC have shown that both the membrane stretch and intracellular Ca(2+) signal allosterically regulate the channel activity via the linker of the gating ring complex. Here we investigate how these two gating principles interact with each other. We found that stretch force activated SAKCaC in the absence of cytoplasmic Ca(2+). Lack of Ca(2+) bowl (a calcium binding motif) in SAKCaC diminished the Ca(2+)-dependent activation, but the mechanosensitivity of channel was intact. We also found that the abrogation of STREX (a proposed mechanosensing apparatus) in SAKCaC abolished the mechanosensitivity without altering the Ca(2+) sensitivity of channels. These observations indicate that membrane stretch and intracellular Ca(2+) could independently modulate SAKCaC activity.
Zhao
Hu-Cheng
HC
Lab of Biomechanics, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, PR China. zhaohc@mail.tsinghua.edu.cn
Agula
Hasi
H
Zhang
Wei
W
Wang
Fa
F
Sokabe
Masahiro
M
Li
Lu-Ming
LM
D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D002645:Chickens; D003593:Cytoplasm / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008958:Models, Molecular; D016296:Mutagenesis; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
D030161:Avian Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D050505:Mutant Proteins; D011994:Recombinant Proteins; D002118:Calcium