Role of protein kinase C in mediating effects of hydrogen peroxide in guinea-pig ventricular myocytes*1

Ward, Christopher A.; Moffat, Margaret P.

doi:10.1016/0022-2828(95)90077-2

Cited by 35 publications

(18 citation statements)

References 33 publications

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“…In normal cardiomyocytes, the cytosolic [Ca 2ϩ ] is 0.1-0.15 M in the resting state, and 0.1-10 M during contraction (38). In pathological conditions such as myocardial ischemia and heart failure, the baseline [Ca 2ϩ ] i during diastole may be increased to cause intracellular Ca 2ϩ overload (7,11,28,35,49). Maltsev and colleagues (25) reported that [Ca 2ϩ ] i at concentration of 1.0 M increased the amplitude of I Na.L in ventricular myocytes isolated from normal and failure dog hearts.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of KN-93 and autocamtide-2-related inhibitory peptide II (2 M) were not different. A combination of overload, is a pathological occurrence in the heart and is reported to be related to ischemia, hypoxia, oxidative stress, cardiac hypertrophy, heart failure, and elevated catecholamine levels (7,11,28,35,49). Intracellular Ca 2ϩ overload results in cardiac mechanical and electrical dysfunction (44).…”

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Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes

Luo

et al. 2012

American Journal of Physiology-Cell Physiology

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[Ca 2ϩ ]i from 0.1 to 0.3, 0.6, and 1.0 M increased I Na.L in a concentration-dependent manner from 0.221 Ϯ 0.038 to 0.554 Ϯ 0.045 pA/pF (n ϭ 10, P Ͻ 0.01) and was associated with an increase in mean Na ϩ channel open probability and prolongation of channel mean open-time (n ϭ 7, P Ͻ 0.01). In the presence of 0.6 M [Ca 2ϩ ]i, KN-93 (10 M) and bisindolylmaleimide (BIM, 2 M) decreased I Na.L by 45.2 and 54.8%, respectively. The effects of KN-93 and autocamtide-2-related inhibitory peptide II (2 M) were not different. A combination of overload, is a pathological occurrence in the heart and is reported to be related to ischemia, hypoxia, oxidative stress, cardiac hypertrophy, heart failure, and elevated catecholamine levels (7,11,28,35,49). Intracellular Ca 2ϩ overload results in cardiac mechanical and electrical dysfunction (44). Many pathological conditions that lead to intracellular Ca 2ϩ overload in ventricular myocytes are also associated with an increase in the late or persistent sodium current (I Na.L ) (1, 17, 18, 21, 23, 24, 26, 40 -42, 47, 48, 53). I Na.L is created when inactivation-resistant sodium channels continue to open for long periods during the action potential plateau. Maltsev et al. (25) reported that an increase in the level of [Ca 2ϩ ] i from baseline to 1 M increased the amplitude of I Na.L in dog ventricular myocytes via a mechanism involving activation of Ca 2ϩ -calmodulin-dependent protein kinase II (CaMKII). Elevated [Ca 2ϩ ] i is also reported to activate protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) (31, 39, 52), and the PKC activation is associated with an increase in I Na.L (3,4,10,14,27,29,48,50,51).An increase in the amplitude of I Na.L may prolong action potential duration, increase the transmural dispersion of repolarization, and cause cardiac arrhythmias (2). An increase in I Na.L also raises the intracellular sodium concentration and subsequently increases [Ca 2ϩ ] i via the reverse mode of the Na ϩ -Ca 2ϩ exchanger to cause further Ca 2ϩ influx (18,20). Reduction of the extracellular Na ϩ concentration or inhibition of I Na.L was shown to attenuate the increase in [Ca 2ϩ ] i (8,12,15,22,32,36,37,43). Inhibition of I Na.L is therefore a potential therapeutic target for the treatment of cardiac arrhythmias and myocardial dysfunction associated with intracellular Ca 2ϩ overload (5,6,16,33,34,45,46). In this study we tested the hypothesis that both CaMKII and PKC mediate the augmentation of I Na.L in the presence of an increased [Ca 2ϩ ] i . Using rabbit ventricular myocytes, we measured whole cell Na ϩ current and single Na ϩ channel activities, the latter with a novel open cell-attached patch technique. I Na.L and single Na ϩ channel activities were investigated under conditions mimicking the physiological and pathological conditions of normal and increased [Ca 2ϩ ] i . In cells with increased [Ca 2ϩ ] i , agents that modulate the functions of CaMKII, PKC, and MAPK were used to determine the relative contributions of these signali...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes

Luo

et al. 2012

American Journal of Physiology-Cell Physiology

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“…Role of PKC in action potential prolongation The finding that H202-induced action potential prolongation is observed only when the perforated patch method is utilized suggests that the intracellular mediator(s) of action of H202 can be altered by dialysis of the myoplasm. Previous reports have demonstrated that in guinea-pig ventricular myocytes, H202-induced changes in intracellular Ca are associated with activation of PKC (Ward & Moffat, 1995). To determine if PKC is involved in the action potential prolongation observed in the current study, 100 nM BIS, a potent PKC inhibitor (Muid et al 1991), was added to the superfusion solution.…”

Section: Involvement Of Ina In Action Potential Prolongationmentioning

confidence: 99%

“…examining the myocardial effects of H202 have demonstrated that H202 can cause lipid peroxidation (Rubin & Farber, 1984), enzyme activation (Natarajan et al 1993;Mekhfi, Veksler, Mateo, Maupoil, Rochette & Ventura-Clapier, 1996), altered energy metabolism (Spragg, Hinshaw, Hyslop, Schraufstatter & Cochrane, 1985), protein oxidation (Fliss, Masika, Eley & Korecky, 1988) and changes in intracellular Ca2+ concentration (Hyslop, Hinshaw, Schraufstatter, Sklar, Spragg & Cochrane, 1986;Ward & Moffat, 1995). Proarrhythmic activity of H202 has also been demonstrated (Beresewicz & Horackova, 1991;Duan & Moffat, 1992).…”

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confidence: 99%

“…This causes the release of diacylglycerol, an endogenous activator of PKC (Nishizuka, 1995). A recent report by Ward & Moffat (1995) demonstrated that in the guinea-pig ventricle the rise in intracellular Ca2+ following H202 exposure was attenuated by inhibitors of PKC. The purpose of the present study was to examine the effects of H202 on whole-cell currents and action potentials in isolated rat ventricular myocytes and to evaluate the involvement of PKC as a second messenger for these electrophysiological effects.…”

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Ionic mechanism of the effects of hydrogen peroxide in rat ventricular myocytes.

Ward

Giles

1997

The Journal of Physiology

184

151

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1. Whole-cell and amphotericin-perforated patch-clamp techniques have been used to study the effects of hydrogen peroxide (H202) on action potentials and underlying ionic currents in single myocytes from the ventricles of adult rat hearts. 2. The results obtained differed markedly depending on the recording method utilized.Conventional 6. The possibility that protein kinase C (PKC) is an intracellular second messenger for the observed effects of H202 was examined using the blocker bisindolylmaelimide (BIS; 10-7 M).Bath application of BIS prior to H202 exposure significantly delayed and also attenuated the development of the action potential prolongation. 7. These results demonstrate marked electrophysiological effects of H202 in rat ventricle.

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Oxidants Depress the Synthesis of Phosphatidylinositol 4,5-Bisphosphate in Heart Sarcolemma

Mesaeli

Tappia

Suzuki

et al. 2000

Archives of Biochemistry and Biophysics

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Role of protein kinase C in mediating effects of hydrogen peroxide in guinea-pig ventricular myocytes*1

Cited by 35 publications

References 33 publications

Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes

Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes

Ionic mechanism of the effects of hydrogen peroxide in rat ventricular myocytes.

Oxidants Depress the Synthesis of Phosphatidylinositol 4,5-Bisphosphate in Heart Sarcolemma

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