Acetylcholine-induced production of reactive oxygen species in adult rabbit ventricular myocytes is dependent on phosphatidylinositol 3- and Src-kinase activation and mitochondrial KATP channel opening

2003 ◽  
Vol 35 (6) ◽  
pp. 653-660 ◽  
Author(s):  
O Oldenburg
Keyword(s):  
Reactive Oxygen Species ◽  
Katp Channel ◽  
Ventricular Myocytes ◽  
Reactive Oxygen ◽  
Adult Rabbit ◽  
Oxygen Species ◽  
Kinase Activation ◽  
Mitochondrial Katp Channel ◽  
Channel Opening ◽  
Rabbit Ventricular Myocytes

scholarly journals Mechano-arrhythmogenicity is enhanced during late repolarisation in ischemia and driven by a TRPA1-, calcium-, and reactive oxygen species-dependent mechanism

2021 ◽  
Author(s):  
Breanne Ashleigh Cameron ◽  
T Alexander Quinn
Keyword(s):  
Reactive Oxygen Species ◽  
Ventricular Myocytes ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cellular Mechanisms ◽  
Sustained Activity ◽  
Intracellular Ca ◽  
Rabbit Ventricular Myocytes ◽  
Induced Changes ◽  
Dependent Mechanism

Background: Cardiac dyskinesis in regional ischemia results in arrhythmias through mechanically-induced changes in electrophysiology ('mechano-arrhythmogenicity') that involve ischemic alterations in voltage-calcium (Ca2+) dynamics, creating a vulnerable period (VP) in late repolarisation. Objective: To determine cellular mechanisms of mechano-arrhythmogenicity in ischemia and define the importance of the VP. Methods and Results: Voltage-Ca2+ dynamics were simultaneously monitored in rabbit ventricular myocytes by dual-fluorescence imaging to assess the VP in control and simulated ischemia (SI). The VP was longer in SI than in control (146±7 vs 54±8 ms; p<0.0001) and was reduced by blocking KATP channels with glibenclamide (109±6 ms; p<0.0001). Cells were rapidly stretched (10-18% increase in sarcomere length over 110-170 ms) with carbon fibres during diastole or the VP. Mechano-arrhythmogenicity, associated with stretch and release in the VP, was greater in SI than control (7 vs 1% of stretches induced arrhythmias; p<0.005) but was similar in diastole. Arrhythmias during the VP were more complex than in diastole (100 vs 69% had sustained activity; p<0.05). In the VP, incidence was reduced with glibenclamide (2%; p<0.05), by chelating intracellular Ca2+ (BAPTA; 2%; p<0.05), blocking mechano-sensitive TRPA1 (HC-030031; 1%; p<0.005), or by scavenging (NAC; 1%; p<0.005) or blocking reactive oxygen species (ROS) production (DPI; 2%; p<0.05). Ratiometric Ca2+ imaging revealed that SI increased diastolic Ca2+ (+9±1%, p<0.0001), which was not prevented by HC-030031 or NAC. Conclusion: In ischemia, mechano-arrhythmogenicity is enhanced specifically during the VP and is mediated by ROS, TRPA1, and Ca2+.

Mitochondrial Adenosine Triphosphate–regulated Potassium Channel Opening Acts as a Trigger for Isoflurane-induced Preconditioning by Generating Reactive Oxygen Species

2003 ◽  
Vol 98 (4) ◽  
pp. 935-943 ◽  
Author(s):  
Katsuya Tanaka ◽  
Dorothee Weihrauch ◽  
Lynda M. Ludwig ◽  
Judy R. Kersten ◽  
Paul S. Pagel ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Infarct Size ◽  
Adenosine Triphosphate ◽  
Superoxide Anion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Superoxide Anion Production ◽  
Channel Opening ◽  
Anion Production

Background Whether the opening of mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels is a trigger or an end effector of anesthetic-induced preconditioning is unknown. We tested the hypothesis that the opening of mitochondrial K(ATP) channels triggers isoflurane-induced preconditioning by generating reactive oxygen species (ROS) in vivo. Methods Pentobarbital-anesthetized rabbits were subjected to a 30-min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive a vehicle (0.9% saline) or the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD) alone 10 min before or immediately after a 30-min exposure to 1.0 minimum alveolar concentration (MAC) isoflurane. In another series of experiments, the fluorescent probe dihydroethidium was used to assess superoxide anion production during administration of 5-HD or the ROS scavengers N-acetylcysteine or N-2-mercaptopropionyl glycine (2-MPG) in the presence or absence of 1.0 MAC isoflurane. Myocardial infarct size and superoxide anion production were measured using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively. Results Isoflurane (P &lt; 0.05) decreased infarct size to 19 +/- 3% (mean +/- SEM) of the left ventricular area at risk as compared to the control (38 +/- 4%). 5-HD administered before but not after isoflurane abolished this beneficial effect (37 +/- 4% as compared to 24 +/- 3%). 5-HD alone had no effect on infarct size (42 +/- 3%). Isoflurane increased fluorescence intensity. Pretreatment with N-acetylcysteine, 2-MPG, or 5-HD before isoflurane abolished increases in fluorescence, but administration of 5-HD after isoflurane only partially attenuated increases in fluorescence produced by the volatile anesthetic agent. Conclusions The results indicate that mitochondrial K(ATP) channel opening acts as a trigger for isoflurane-induced preconditioning by generating ROS in vivo.

scholarly journals Reactive oxygen species inhibit vascular KATP channel via S‐glutathionylation

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Yang Yang ◽  
Weiwei Shi ◽  
Ningren Cui ◽  
Xianfeng Chen ◽  
Yinwei Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Katp Channel ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Vascular Katp Channel

ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel

2003 ◽  
Vol 284 (1) ◽  
pp. H299-H308 ◽  
Author(s):  
Gilles Lebuffe ◽  
Paul T. Schumacker ◽  
Zuo-Hui Shao ◽  
Travis Anderson ◽  
Hirotoro Iwase ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Methyl Ester ◽  
Katp Channel ◽  
Channel Blocker ◽  
No Synthase ◽  
Oxygen Species ◽  
Channel Activation ◽  
Mitochondrial Katp Channel ◽  
The Relationship

Reactive oxygen species (ROS) and nitric oxide (NO) are implicated in induction of ischemic preconditioning. However, the relationship between these oxidant signals and opening of the mitochondrial ATP-dependent potassium (KATP) channel during early preconditioning is not fully understood. We observed preconditioning protection by hypoxia, exogenous H2O2, or PKC activator PMA in cardiomyocytes subjected to 1-h ischemia and 3-h reperfusion. Protection was abolished by KATP channel blocker 5-hydroxydecanoate (5-HD) in each case, indicating that these triggers must act upstream from the KATP channel. Inhibitors of NO synthase abolished protection in preconditioned cells, suggesting that NO is also required for protection. DAF-2 fluorescence (NO sensitive) increased during hypoxic triggering. This was amplified by pinacidil and inhibited by 5-HD, indicating that NO is generated subsequent to KATP channel activation. Exogenous NO during the triggering phase conferred protection blocked by 5-HD. Exogenous NO also restored protection abolished by 5-HD or N ω-nitro-l-arginine methyl ester in preconditioned cells. Antioxidants given during pinacidil or NO triggering abolished protection, confirming that ROS are generated by KATP channel activation. Coadministration of H2O2 and NO restored PMA-induced protection in 5-HD-treated cells, indicating that ROS and NO are required downstream from the KATP channel. We conclude that ROS can trigger preconditioning by causing activation of the KATP channel, which then induces generation of ROS and NO that are both required for preconditioning protection.

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