title: Nucleotides maintain the activity of Cav1.2 channels in guinea-pig ventricular myocytes.
abstract: The activity of Cav1.2 Ca(2+) channels is maintained in the presence of calmodulin and ATP, even in cell-free patches, and thus a channel ATP-binding site has been suggested. In this study, we examined whether other nucleotides, such as GTP, UTP, CTP, ADP and AMP, could be substituted for ATP in guinea-pig ventricular myocytes. We found that all the nucleotides tested could re-prime the Ca(2+) channels in the presence of 1 μM calmodulin in the inside-out mode. The order of efficacy was ATP > GTP > UTP > ADP > CTP ≈ AMP. Thus, the presumed nucleotide-binding site in the channel seemed to favor a purine rather than pyrimidine base and a triphosphate rather than a di- or mono-phosphate group. Furthermore, a high concentration (10 mM) of GTP, UTP, CTP, ADP and AMP had inhibitory effects on the channel activity. These results provide information on the putative nucleotide-binding site(s) in Cav1.2 Ca(2+) channels.
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China; Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Shu-yuan
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Xu
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: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Qing-hua
authors.initials: QH
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, 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 110122, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China.
authors.forename: Mei-mi
authors.initials: MM
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China; Cardiovascular Institute of China Medical University, Shenyang 110001, China. Electronic address: lyhao@mail.cmu.edu.cn.
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Hao
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
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009711:Nucleotides / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D009711:Nucleotides
keywords: ATP; Binding site; Ca(2+) channel; Cav1.2; Nucleotide