Mechanisms underlying the modulation of L-type Ca2+ channel by hydrogen peroxide in guinea pig ventricular myocytes. 2013

Lei Yang, and Jianjun Xu, and Etsuko Minobe, and Lifeng Yu, and Rui Feng, and Asako Kameyama, and Kazuto Yazawa, and Masaki Kameyama
Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima, 890-8544, Japan.

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.

UI MeSH Term Description Entries
D003545 Cysteine A thiol-containing non-essential amino acid that is oxidized to form CYSTINE. Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D005260 Female Females
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006861 Hydrogen Peroxide A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001596 Benzylamines Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group. Phenylmethylamine,alpha-Aminotoluene,alpha Aminotoluene
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D054732 Calcium-Calmodulin-Dependent Protein Kinase Type 2 A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Ca(2+)-Calmodulin Dependent Protein Kinase Type II,CaCMKII,CaM KII,CaM KIIalpha,CaM KIIbeta,CaM KIIdelta,CaM Kinase II,CaM Kinase II alpha,CaM Kinase II beta,CaM Kinase II delta,CaM Kinase II gamma,CaM PK II,CaM-Kinase II,CaM-Kinase IIalpha,CaMKII,CaMKIIgamma,Calcium-Calmodulin Dependent Protein Kinase II beta,Calcium-Calmodulin Dependent Protein Kinase II delta,Calcium-Calmodulin Dependent Protein Kinase II gamma,Calcium-Calmodulin Protein Kinase II,Calcium-Calmodulin-Dependent PK Type II,Calcium-Calmodulin-Dependent Protein Kinase Type 2 alpha Subunit,Calcium-Calmodulin-Dependent Protein Kinase Type 2 beta Subunit,Calcium-Calmodulin-Dependent Protein Kinase Type 2 delta Subunit,Calcium-Calmodulin-Dependent Protein Kinase Type 2 gamma Subunit,Calcium-Dependent CaM Kinase II,Calmodulin Kinase IIalpha,Calmodulin-Dependent Protein Kinase II,CaM Kinase IIalpha,Calcium Calmodulin Dependent PK Type II,Calcium Calmodulin Dependent Protein Kinase II beta,Calcium Calmodulin Dependent Protein Kinase II delta,Calcium Calmodulin Dependent Protein Kinase II gamma,Calcium Calmodulin Dependent Protein Kinase Type 2,Calcium Calmodulin Dependent Protein Kinase Type 2 alpha Subunit,Calcium Calmodulin Dependent Protein Kinase Type 2 beta Subunit,Calcium Calmodulin Dependent Protein Kinase Type 2 delta Subunit,Calcium Calmodulin Dependent Protein Kinase Type 2 gamma Subunit,Calcium Calmodulin Protein Kinase II,Calcium Dependent CaM Kinase II,Calmodulin Dependent Protein Kinase II
D018408 Patch-Clamp Techniques An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used. Patch Clamp Technique,Patch-Clamp Technic,Patch-Clamp Technique,Voltage-Clamp Technic,Voltage-Clamp Technique,Voltage-Clamp Techniques,Whole-Cell Recording,Patch-Clamp Technics,Voltage-Clamp Technics,Clamp Technique, Patch,Clamp Techniques, Patch,Patch Clamp Technic,Patch Clamp Technics,Patch Clamp Techniques,Recording, Whole-Cell,Recordings, Whole-Cell,Technic, Patch-Clamp,Technic, Voltage-Clamp,Technics, Patch-Clamp,Technics, Voltage-Clamp,Technique, Patch Clamp,Technique, Patch-Clamp,Technique, Voltage-Clamp,Techniques, Patch Clamp,Techniques, Patch-Clamp,Techniques, Voltage-Clamp,Voltage Clamp Technic,Voltage Clamp Technics,Voltage Clamp Technique,Voltage Clamp Techniques,Whole Cell Recording,Whole-Cell Recordings
D020746 Calcium Channels, L-Type Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and non-excitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites. Dihydropyridine Receptors,L-Type Calcium Channels,L-Type VDCC alpha-1 Subunit,L-Type Voltage-Dependent Calcium Channel,Long-Lasting Calcium Channel,Long-Lasting Calcium Channels,Receptors, Dihydropyridine,Dihydropyridine Receptor,L-Type Calcium Channel,L-Type VDCC,L-Type VDCC alpha-2 Subunit,L-Type VDCC beta Subunit,L-Type VDCC delta Subunit,L-Type VDCC gamma Subunit,L-Type Voltage-Dependent Calcium Channels,Calcium Channel, L-Type,Calcium Channel, Long-Lasting,Calcium Channels, L Type,Calcium Channels, Long-Lasting,Channel, Long-Lasting Calcium,L Type Calcium Channel,L Type Calcium Channels,L Type VDCC,L Type VDCC alpha 1 Subunit,L Type VDCC alpha 2 Subunit,L Type VDCC beta Subunit,L Type VDCC delta Subunit,L Type VDCC gamma Subunit,L Type Voltage Dependent Calcium Channel,L Type Voltage Dependent Calcium Channels,Long Lasting Calcium Channel,Long Lasting Calcium Channels,Receptor, Dihydropyridine,VDCC, L-Type

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