title: Calmodulin kinase II activation is required for the maintenance of basal activity of L-type Ca2+ channels in guinea-pig ventricular myocytes.
abstract: The roles of calmodulin (CaM)-dependent protein kinase II (CaMKII) in the maintenance of basal activity and the reversion of run-down of L-type Ca2+ channels were studied in guinea-pig ventricular myocytes by the patch-clamp technique. In the cell-attached configuration, the Ca2+-channel activity was inhibited to 82% - 26% by 1-10 microM KN-93 and to 92% - 66% by 0.1-1 microM autocamtide-2-related inhibitory peptide (AIP) myristoylated. In the inside-out configuration, the bovine cardiac cytoplasm recovered Ca2+-channel activity to 87% of that recorded in the cell-attached configuration, while the CaMKII inhibitor 281-301 at 10 microM reduced the recovery effect to 19%. CaM + ATP recovered the channel activity to 93% and 28% of that recorded in the cell-attached configuration when applied at 1 and 5 min after run-down, respectively, showing a time-dependent attenuation. However, in the presence of 0.33 microM CaMKII, this attenuation was abolished, showing 85% and 75% recovery when applied at 1 and 5 min after run-down, respectively. This recovery effect was suppressed by 10 microM AIP, applied at 5 min, but not at 1 min after run-down. We concluded that CaMKII activation is required in the maintenance of basal activity of L-type Ca2+ channels.
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacological Sciences, China Medical University, Shenyang, China. lyhao@mail.cmu.edu.cn
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Hao
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Xu
authors.forename: Etsuko
authors.initials: E
authors.lastname: Minobe
authors.forename: Asako
authors.initials: A
authors.lastname: Kameyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Kameyama
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D002417:Cattle; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000201:enzymology; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology*; D018408:Patch-Clamp Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013997:Time Factors
chemical_list: D020746:Calcium Channels, L-Type; D002147:Calmodulin; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2