naa a22 4500 510805604 CHVBK 20180411083416.0 cr unu---uuuuu 180411e20131101xx s 000 0 eng 10.1007/s12576-013-0279-2 doi (NATIONALLICENCE)springer-10.1007/s12576-013-0279-2 Mechanisms underlying the modulation of L-type Ca2+ channel by hydrogen peroxide in guinea pig ventricular myocytes [Elektronische Daten] [Lei Yang, Jianjun Xu, Etsuko Minobe, Lifeng Yu, Rui Feng, Asako Kameyama, Kazuto Yazawa, Masaki Kameyama] Although Cav1.2 Ca2+ 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 Ca2+ channel using a patch-clamp technique in guinea pig ventricular myocytes. Externally applied H2O2 (1mM) increased Ca2+ channel activity in the cell-attached mode. A specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII) KN-93 (10μM) partially attenuated the H2O2-mediated facilitation of the channel, suggesting both CaMKII-dependent and -independent pathways. However, in the inside-out mode, 1mM 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 Ca2+ channel itself. A thiol-specific oxidizing agent mimicked and occluded the H2O2 effect. These results suggest that H2O2 facilitates the Ca2+ channel through oxidation of cysteine residue(s) in the channel as well as the CaMKII-dependent pathway. The Physiological Society of Japan and Springer Japan, 2013 Calcium channel nationallicence Reactive oxygen species nationallicence H2O2 nationallicence Calmodulin nationallicence Cardiac myocytes nationallicence Yang Lei Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut Xu Jianjun Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut Minobe Etsuko Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut Yu Lifeng Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut Feng Rui Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut Kameyama Asako Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut Yazawa Kazuto Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut Kameyama Masaki Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut The Journal of Physiological Sciences Springer Japan 63/6(2013-11-01), 419-426 1880-6546 63:6<419 2013 63 12576 https://doi.org/10.1007/s12576-013-0279-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12576-013-0279-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Lei Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Xu Jianjun Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Minobe Etsuko Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Yu Lifeng Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Feng Rui Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Kameyama Asako Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Yazawa Kazuto Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Kameyama Masaki Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 773 0- The Journal of Physiological Sciences Springer Japan 63/6(2013-11-01), 419-426 1880-6546 63:6<419 2013 63 12576 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer