title: Mechanisms underlying the modulation of L-type Ca2+ channel by hydrogen peroxide in guinea pig ventricular myocytes.
abstract: Although Cav1.2 Ca(2+) channels are modulated by reactive oxygen species (ROS), the underlying mechanisms are not fully understood. In this study, we investigated effects of hydrogen peroxide (H2O2) on the Ca(2+) channel using a patch-clamp technique in guinea pig ventricular myocytes. Externally applied H2O2 (1 mM) increased Ca(2+) channel activity in the cell-attached mode. A specific inhibitor of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) KN-93 (10 μM) partially attenuated the H2O2-mediated facilitation of the channel, suggesting both CaMKII-dependent and -independent pathways. However, in the inside-out mode, 1 mM H2O2 increased channel activity in a KN-93-resistant manner. Since H2O2-pretreated calmodulin did not reproduce the H2O2 effect, the target of H2O2 was presumably assigned to the Ca(2+) channel itself. A thiol-specific oxidizing agent mimicked and occluded the H2O2 effect. These results suggest that H2O2 facilitates the Ca(2+) channel through oxidation of cysteine residue(s) in the channel as well as the CaMKII-dependent pathway.
authors.affiliation: Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima, 890-8544, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xu
authors.forename: Etsuko
authors.initials: E
authors.lastname: Minobe
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.forename: Asako
authors.initials: A
authors.lastname: Kameyama
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yazawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Kameyama
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D003545:Cysteine / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D020746:Calcium Channels, L-Type; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003545:Cysteine; D006861:Hydrogen Peroxide; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides