MitoKATP channel activation suppresses gap junction permeability in the ischemic myocardium by an ERK-dependent mechanism

Naitoh, Kazuyuki; Ichikawa, Yoshihiko; Miura, Tetsuji; Nakamura, Yūichi; Miki, Takayuki; Ikeda, Yoshihiro; Kobayashi, Hironori; Nishihara, Masahiro; Ohori, Katsuhiko; Shimamoto, Kazuaki

doi:10.1016/j.cardiores.2006.01.023

Cited by 37 publications

(41 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Sprague-Dawley rats of 8ϳ10 wk of age were anesthetized by pentobarbital sodium (40 mg/kg ip injection), intubated, and mechanically ventilated with a Harvard rodent ventilator using oxygen supplement. Hearts were excised, quickly mounted on a Langendorff apparatus, and perfused with modified KrebsHenseleit buffer as previously reported (20,21). Perfusion pressure and temperature of the perfusate were maintained at 75 mmHg and 38°C, respectively.…”

Section: Experiments I: Ip-immunoblotting Experimentsmentioning

confidence: 99%

“…IP of Cx43 and immunoblotting for kinases were performed as in our previous studies (20,21). In brief, tissues were homogenized in ice-cold Tris buffer containing 20 mM Tris ⅐ HCl, 1 mM EGTA, 5 mM NaN 3, 50 mM NaCl, 1 mM phenylmethylsulfonyl fluoride (PMSF), 50 mM Na3VO4, and a protease inhibitor cocktail (Complete Mini; Roche Diagnostics, Manheim, Germany).…”

Section: Experiments I: Ip-immunoblotting Experimentsmentioning

confidence: 99%

“…The contribution of PC-induced gap junction blockade to myocardial protection is difficult to assess since there is no selective and direct opener of closed gap junctions. However, there are several lines of circumstantial evidence suggesting that chemical uncoupling of the gap junction during ischemiareperfusion is a part of the mechanism of infarct size limitation afforded by PC: infarct size-limiting effects of structurally different gap junction blockers (7,19,20,26), suppression of gap junction permeability by PC mimetics (20,21), and partial loss of protection afforded by a ␦-opioid receptor agonist when suppression of gap junction permeability was abrogated (20). In addition to myocardial necrosis, arrhythmias during ischemia-reperfusion are suppressed by PC (6,24,25), which is possibly associated with alteration in electrical coupling of cardiomyocytes (6,13,24).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning

Naitoh¹,

Yano²,

Miura³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Ischemic preconditioning (PC) suppresses chemical coupling of cardiomyocytes via gap junctions (GJs) during ischemia, which is an adjunct mechanism of protection. The aim of this study was to characterize roles of protein kinases in PC-induced GJ modulation. In isolated rat hearts, ventricular tissues were sampled before and after ischemia with or without PC, and intercalated disc-rich fractions were separated for immunoprecipitation and immunoblotting. Levels of protein kinase C (PKC)-ε, p38mitogen-activated protein kinase (MAPK)-α, and Src coimmunoprecipitated with connexin-43 (Cx43) were increased after ischemia, whereas p38MAPKβ was not detected in the Cx43 immunoprecipitates. PC did not modify the level of Cx43-Src complex after ischemia. However, PC enhanced Cx43-PKCε complex formation, which was abolished by PKCε translocation inhibitory peptide (TIP). In contrast, PC reduced Cx43-p38MAPKα complex level and p38MAPK activity in the Cx43 immunoprecipitates after ischemia. The effect of PC on Cx43-p38MAPKα interaction was mimicked by SB-203580, a p38MAPK inhibitor. PC reduced permeability of GJs to Lucifer yellow in the myocardium at 25 min after ischemia, and this effect was abolished by PKCε-TIP. SB-203580 increased the GJ permeability at 15 min after ischemia compared with that in untreated controls, but the difference became insignificant 25 min after ischemia. In conclusion, PC has distinct effects on interaction of GJ Cx43 with PKCε, p38MAPKα, and Src during ischemia. Suppression of GJ permeability during ischemia by PC is primarily achieved by enhanced interaction of Cx43 with PKCε, which overwhelms the counterbalancing effect of reduced Cx43-p38MAPKα interaction.

show abstract

Section: Experiments I: Ip-immunoblotting Experimentsmentioning

confidence: 99%

Section: Experiments I: Ip-immunoblotting Experimentsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning

Naitoh¹,

Yano²,

Miura³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…The alteration in the expression level and spatial distribution of Cx43 in the hypertrophic myocardium suggests that this protein is influenced by ventricular remodeling (18). Naitoh et al (26) proposed that the mitoK ATP channel was one of the mechanisms regulating GJ permeability, thus leading to cardioprotective effects against ischemia. Previous studies have reported that decreasing Cx43 expression in the myocardium results in high susceptibility to arrythmogenesis (18,25).…”

Section: A B C D Ementioning

confidence: 99%

Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist

Sun

Wang

Hao

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Cardiac hypertrophy is a compensatory mechanism that occurs in conjunction with cardiovascular diseases. Although hypertrophy of the myocardium provides certain benefits during the early stages of cardiovascular disease, prolonged hypertrophy is potentially harmful to the heart and can result in arrhythmia and heart failure. The aim of this study was to investigate whether an ATP-sensitive K + (K ATP ) channel agonist was capable of reducing isoproterenol (Iso)-induced cardiac hypertrophy and modulating myocardial connexin43 (Cx43) expression. Fifty male Sprague Dawley rats were randomly assigned to five groups: Normal, vehicle, nicorandil, glibenclamide and nicorandil plus glibenclamide. Rats in the four treatment groups received Iso injection for seven days, followed by administration with saline, nicorandil, glibenclamide or a combination of nicorandil and glibenclamide, respectively, for four weeks. Cardiac hypertrophy was then evaluated by measuring body weight, heart weight and left-ventricular weight, and plasma B-type natriuretic peptide levels were evaluated by ELISA. Immunocytochemistry and a reverse transcription-polymerase chain reaction were performed to detect the spatial distribution and gene expression of myocardial Cx43, respectively. The K ATP channel agonist nicorandil markedly attenuated the degree of myocardial hypertrophy induced by Iso as compared with the vehicle group. Myocardial Cx43 expression was significantly decreased and redistributed following cardiac hypertrophy. The decrease and redistribution of Cx43 was reduced following treatment with the K ATP channel agonist nicorandil. Addition of the K ATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43.In conclusion, the present study indicated that chronic use of K ATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43.

show abstract

“…There is even less information available as concerns the relationship between ROS, mitoK ATP channels and arrhythmias. It is suggested that the antiarrhythmic effect of the opening mitoK ATP channels involves the ROS activated ERK pathway which reduces gap junction permeability by the phophorylation of connexin 43 [66]. Although in a previous study we have found that in anaesthetised dogs the administration of ROS scavenging N-2-mercaptopropionylglycine did not modify the antiarrhythmic effect of PC [60], the role of ROS in the PC-induced cardioprotection cannot be ruled out.…”

Section: The Role Of Reactive Oxygen Species In Preconditioningmentioning

confidence: 95%

The antiarrhythmic effect of exogenous peroxynitrite and preconditioning: the involvement of nitric oxide, superoxide and peroxynitrite

Kiss

View full text Add to dashboard Cite

Full papersIWe showed, that compared to the controls, two 5 min periods of the 100 nM concentration of PN, similar to the same periods of preconditioning ischaemia, markedly reduced the severity of arrhythmias and attenuated the generation of NT that resulted from a 25 min occlusion and reperfusion of the left anterior descending coronary artery. Since these effects were not modified by the prior administration of 5-HD, we concluded that, in contrast to PC, the antiarrhythmic effect of PN does not involve the opening of mitoK ATP channels.However, the observed attenuation in I/R-induced NT formation following PC and PN has promted us to examine, whether this results from a reduced NO or from a reduced O 2 . production. Therefore, in another series of experiments we measured changes in plasma and tissue nitrate/nitrite (NOx, a biomarker of NO production), O 2 . and NT productions in control, in PC and in PN treated dogs. We have found that in contrast to the controls in which the plasma NOx levels were markedly decreased by the end of the occlusion, in dogs subjected to PC and PN infusion NOx levels were maintained over the entire ischaemic period.

show abstract

MitoKATP channel activation suppresses gap junction permeability in the ischemic myocardium by an ERK-dependent mechanism

Abstract: Opening of the mitoKATP channel activates ERK1/2 via free radicals and induces ERK-mediated suppression of GJ permeability. This suppression of GJ permeability may partly contribute to cardioprotection afforded by mitoKATP channel activation.

Cited by 37 publications

References 35 publications

Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning

Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning

Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist

The antiarrhythmic effect of exogenous peroxynitrite and preconditioning: the involvement of nitric oxide, superoxide and peroxynitrite

Contact Info

Product

Resources

About