Membrane stretch and cytoplasmic Ca2+ independently modulate stretch-activated BK channel activity |
| |
| Authors: | Hu-cheng Zhao Hasi Agula Wei Zhang Fa Wang Masahiro Sokabe Lu-ming Li |
| |
| Institution: | 1. Lab of Biomechanics, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, PR China;2. College of Life Science of Inner Mongolia University, Inner Mongolia, PR China;3. Department of Physiology, Nagoya University Graduate School of Medicine, Tsurumai, Nagoya 466-8550, Japan;1. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK;2. Institut de Neurociències and Dept. Bioquímica i Biol. Mol., Universitat Autònoma de Barcelona, Edifici M, Campus Bellaterra, E-08193 Cerdanyola del Vallès, Barcelona, Catalonia, Spain;1. Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong;2. Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong;3. School of Aerospace, Tsinghua University, China;1. Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3;2. Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Frederik Bajers Vej 7D3, 9220 Aalborg East, Denmark;3. Dipartimento di Scienze farmacologiche e biomolecolari, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milano, Italy;1. Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autonoma de Mexico, Avenida Universidad, 2001, Cuernavaca, Morelos, 62210, Mexico;2. Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, 04510, Mexico;3. Department of Biophysics and Cell Biology, Faculty of Medicine, Research Center for Molecular Medicine, University of Debrecen, 1 Egyetem ter, Debrecen, 4032, Hungary;1. Department of Medicine, Research Center, Montreal Heart Institute, University of Montreal, 5000 Belanger Street East, Montreal, Quebec H1T 1C8, Canada;2. Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montréal, Québec H3G 1Y6, Canada;3. Faculty of Medicine, University Duisburg-Essen, Hufelandstr. 55, Essen 45122, Germany |
| |
| Abstract: | Large conductance Ca2+-activated K+ (BK) channels are responsible for changes in chemical and physical signals such as Ca2+, Mg2+ 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 Ca2+ 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 Ca2+. Lack of Ca2+ bowl (a calcium binding motif) in SAKCaC diminished the Ca2+-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 Ca2+ sensitivity of channels. These observations indicate that membrane stretch and intracellular Ca2+ could independently modulate SAKCaC activity. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
