title: A Role of BK Channel in Regulation of Ca2+Channel in Ventricular Myocytes by Substrate Stiffness.
abstract: Substrate stiffness is crucial for diverse cell functions, but the mechanisms conferring cells with mechanosensitivity are still elusive. By tailoring substrate stiffness with 10-fold difference, we showed that L-type voltage-gated Ca2+channel current density was greater in chick ventricular myocytes cultured on the stiff substrate than on the soft substrate. Blockage of the BK channel increased the Ca2+current density on the soft substrate and consequently eliminated substrate stiffness regulation of the Ca2+channel. The expression of the BK channel, including the STREX-containing α-subunit that forms stretch-activated BK channel in myocytes and the BK channel function in myocytes (and also in HEK293 cells heterologously expressing STREX-containing α- and β1-subunits) was reduced in cells cultured on the stiff substrate. Furthermore, in HEK293 cells coexpressing the cardiac CaV1.2 channel and STREX-containing BK channel, the Ca2+current density was greater in cells on the stiff substrate, which was not observed in cells expressing the CaV1.2 channel alone or coexpressing with the STREX-deleted BK channel. These results provide strong evidence to show that the stretch-activated BK channel plays a key role in functional regulation of cardiac voltage-gated Ca2+channel by substrate stiffness, revealing, to our knowledge, a novel mechanosensing mechanism in ventricular myocytes.
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China.
authors.forename: Hucheng
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China.
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China.
authors.forename: Bailin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China. Electronic address: libome@mail.tsinghua.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds, United Kingdom; Department of Physiology and Neurobiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China. Electronic address: l.h.jiang@leeds.ac.uk.
authors.forename: Linhua
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China. Electronic address: fengxq@mail.tsinghua.edu.cn.
authors.forename: Xiqiao
authors.initials: X
authors.lastname: Feng
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002642:Chick Embryo; D004129:Dimethylpolysiloxanes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004560:Electricity; D057809:HEK293 Cells; D006352:Heart Ventricles / Q000166:cytology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D004129:Dimethylpolysiloxanes; D051036:Large-Conductance Calcium-Activated Potassium Channels; D021122:Protein Subunits; D009218:Myosins; D002118:Calcium