title: Calmodulin- and Ca2+-dependent facilitation and inactivation of the Cav1.2 Ca2+ channels in guinea-pig ventricular myocytes.
abstract: The L-type Ca(2+) channel (Ca(V)1.2) shows clear Ca(2+)-dependent facilitation and inactivation. Here we have examined the effects of calmodulin (CaM) and Ca(2+) on Ca(2+) channel in guinea-pig ventricular myocytes in the inside-out patch mode, where rundown of the channels was controlled. At a free [Ca(2+)] of 0.1 microM, CaM (0.15, 0.7, 1.4, 2.1, 3.5, and 7.0 microM) + ATP (2.4 mM) induced channel activities of 27%, 98%, 142%, 222%, 65%, and 20% relative to the control activity, respectively, showing a bell-shaped relationship. Similar results were observed at a free [Ca(2+)] <0.01 microM or with a Ca(2+)-insensitive mutant, CaM(1234), suggesting that apoCaM may induce facilitation and inactivation of the channel activity. The bell-shaped curve of CaM was shifted to the lower concentration side with increasing [Ca(2+)]. A simple model for CaM- and Ca(2+)-dependent modulations of the channel activity, which involves two CaM-binding sites, was proposed. We suggest that both apoCaM and Ca(2+)/CaM can induce facilitation and inactivation of Ca(V)1.2 Ca(2+) channels and that the basic role of Ca(2+) is to accelerate CaM-dependent facilitation and inactivation.
authors.affiliation: School of Pharmaceutical Science, China Medical University, Shenyang, China.
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Han
authors.forename: Etsuko
authors.initials: E
authors.lastname: Minobe
authors.forename: Wu-Yang
authors.initials: WY
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Xu
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Hao
authors.forename: Masaki
authors.initials: M
authors.lastname: Kameyama
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002147:Calmodulin / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002147:Calmodulin; C419385:L-type calcium channel alpha(1C); D002118:Calcium