title: Extrapolating microdomain Ca(2+) dynamics using BK channels as a Ca(2+) sensor.
abstract: Ca(2+) ions play crucial roles in mediating physiological and pathophysiological processes, yet Ca(2+) dynamics local to the Ca(2+) source, either from influx via calcium permeable ion channels on plasmic membrane or release from internal Ca(2+) stores, is difficult to delineate. Large-conductance calcium-activated K(+) (BK-type) channels, abundantly distribute in excitable cells and often localize to the proximity of voltage-gated Ca(2+) channels (VGCCs), spatially enabling the coupling of the intracellular Ca(2+) signal to the channel gating to regulate membrane excitability and spike firing patterns. Here we utilized the sensitivity and dynamic range of BK to explore non-uniform Ca(2+) local transients in the microdomain of VGCCs. Accordingly, we applied flash photolysis of caged Ca(2+) to activate BK channels and determine their intrinsic sensitivity to Ca(2+). We found that uncaging Ca(2+) activated biphasic BK currents with fast and slow components (time constants being τf ≈ 0.2 ms and τs ≈ 10 ms), which can be accounted for by biphasic Ca(2+) transients following light photolysis. We estimated the Ca(2+)-binding rate constant kb (≈1.8 × 10(8)  M(-1) s(-1)) for mSlo1 and further developed a model in which BK channels act as a calcium sensor capable of quantitatively predicting local microdomain Ca(2+) transients in the vicinity of VGCCs during action potentials.
authors.affiliation: Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.|Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, MO 63130, USA.
authors.forename: Panpan
authors.initials: P
authors.lastname: Hou
authors.affiliation: Key Laboratory of Image Processing and Intelligent Control, Huazhong University of Science and Technology, Ministry of Education, Department of Biomedical Engineering, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Image Processing and Intelligent Control, Huazhong University of Science and Technology, Ministry of Education, Department of Biomedical Engineering, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yuchi
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, MO 63130, USA.
authors.forename: Guohui
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Image Processing and Intelligent Control, Huazhong University of Science and Technology, Ministry of Education, Department of Biomedical Engineering, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, MO 63130, USA.|Department of pharmacology, Soochow University college of pharmaceutical Sciences, Suzhou, 215123, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Cui
authors.affiliation: Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Program in Neurosciences and Mental Health, SickKids Research Institute &Department of Physiology, University of Toronto, Toronto, Canada M5G 1X8.
authors.forename: Lu-Yang
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.
authors.forename: Jiuping
authors.initials: J
authors.lastname: Ding
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000235:genetics; D018408:Patch-Clamp Techniques; D010782:Photolysis
chemical_list: D015220:Calcium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium