title: Both N- and C-lobes of calmodulin are required for Ca2+-dependent regulations of CaV1.2 Ca2+ channels.
abstract: We investigated the concentration- and Ca(2+)-dependent effects of CaM mutants, CaM(12) and CaM(34), in which Ca(2+)-binding to its N- and C-lobes was eliminated, respectively, on the Ca(V)1.2 Ca(2+) channel by inside-out patch clamp in guinea-pig cardiomyocytes. Both CaM(12) and CaM(34) (0.7-10muM) applied with 3mM ATP produced channel activity after "rundown". Concentration-response curves were bell-shaped, similar to that for wild-type CaM. However, there was no obvious leftward shift of the curves by increasing [Ca(2+)], suggesting that both functional lobes of CaM were necessary for the Ca(2+)-dependent shift. However, channel activity induced by the CaM mutants showed Ca(2+)-dependent decrease, implying a Ca(2+) sensor existing besides CaM. These results suggest that both N- and C-lobes of CaM are required for the Ca(2+)-dependent regulations of Ca(V)1.2 Ca(2+) channels.
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, 92 Beier Road, Shenyang 110001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Etsuko
authors.initials: E
authors.lastname: Minobe
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yazawa
authors.forename: Hadhimulya
authors.initials: H
authors.lastname: Asmara
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Bai
authors.forename: Dong-yun
authors.initials: DY
authors.lastname: Han
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Hao
authors.forename: Masaki
authors.initials: M
authors.lastname: Kameyama
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D020746:Calcium Channels, L-Type; D002147:Calmodulin; C419385:L-type calcium channel alpha(1C); D002118:Calcium