title: The individual N- and C-lobes of calmodulin tether to the Cav1.2 channel and rescue the channel activity from run-down in ventricular myocytes of guinea-pig heart.
abstract: The present study examined the binding of the individual N- and C-lobes of calmodulin (CaM) to Cav1.2 at different Ca(2+) concentration ([Ca(2+)]) from ≈ free to 2mM, and found that they may bind to Cav1.2 Ca(2+)-dependently. In particular, using the patch-clamp technique, we confirmed that the N- or C-lobes can rescue the basal activity of Cav1.2 from run-down, demonstrating the functional relevance of the individual lobes. The data imply that at resting [Ca(2+)], CaM may tether to the channel with its single lobe, leading to multiple CaM molecule binding to increase the grade of Ca(2+)-dependent regulation of Cav1.2.
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Shao
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China.
authors.forename: Meimi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China.
authors.forename: Guilin
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Suyuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Laboratory of Environmental Biology, Northeastern University, Shenyang 110004, China.
authors.forename: Yaonan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Minobe
authors.affiliation: Laboratory of Environmental Biology, Northeastern University, Shenyang 110004, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan. Electronic address: kame@m.kufm.kagoshima-u.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kameyama
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China. Electronic address: lyhao@mail.cmu.edu.cn.
authors.forename: Liying
authors.initials: L
authors.lastname: Hao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D006168:Guinea Pigs; D057809:HEK293 Cells; D006352:Heart Ventricles / Q000166:cytology* / Q000503:physiopathology; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D002147:Calmodulin; C419385:L-type calcium channel alpha(1C); D002118:Calcium
keywords: C-lobe; Ca(2+); Calmodulin; Cav1.2; N-lobe; Patch clamp