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• W1517428658 abstract "New Findings What is the central question of this study? What are the effects of protein kinase C (PKC) and Ca 2+ –calmodulin‐dependent protein kinase II (CaMKII) on late sodium current ( I NaL ), reverse Na + –Ca 2+ exchange current (reverse I NCX ) or intracellular Ca 2+ levels changed by ouabain? What is the main finding and its importance? Ouabain, even at low concentrations (0.5–8.0 μ m ), can increase I NaL and reverse I NCX , and these effects may contribute to the effect of the glycoside to increase Ca 2+ transients and contractility. Both PKC and CaMKII activities may mediate or modulate these processes. It has been reported that the cardiac glycoside ouabain can increase the late sodium current ( I NaL ), as well as the diastolic intracellular calcium concentration and contractile shortening. Whether an increase of I NaL participates in a pathway that can mediate the positive inotropic response to ouabain is unknown. We therefore determined the effects of ouabain on I NaL , reverse Na + –Ca 2+ exchange current (reverse I NCX ), intracellular Ca 2+ ([Ca 2+ ] i ) levels and contractile shortening in rabbit isolated ventricular myocytes. Ouabain (0.1–8 μ m ) markedly increased I NaL and reverse I NCX in a concentration‐dependent manner, with significant effects at concentrations as low as 0.5 and 1 μ m . These effects of ouabain were suppressed by the I NaL inhibitors TTX and ranolazine, the protein kinase C inhibitor bisindolylmaleimide and the Ca 2+ –calmodulin‐dependent protein kinase II inhibitor KN‐93. The enhancement by 0.5 μ m ouabain of ventricular myocyte contractility and intracellular Ca 2+ transients was suppressed by 2.0 μ m TTX. We conclude that ouabain, even at low concentrations (0.5–8.0 μ m ), can increase I NaL and reverse I NCX , and these effects may contribute to the effect of the glycoside to increase Ca 2+ transients and contractility. Both protein kinase C and Ca 2+ –calmodulin‐dependent protein kinase II activities may mediate or modulate these processes." @default.
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• W1517428658 date "2015-03-10" @default.
• W1517428658 modified "2023-10-03" @default.
• W1517428658 title "Protein kinase C and Ca²⁺-calmodulin-dependent protein kinase II mediate the enlarged reverse<i>I</i>_NCXinduced by ouabain-increased late sodium current in rabbit ventricular myocytes" @default.
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• W1517428658 doi "https://doi.org/10.1113/expphysiol.2014.083972" @default.
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