Back to Search
Start Over
Protein kinase C and Ca2+-calmodulin-dependent protein kinase II mediate the enlarged reverse INCX induced by ouabain-increased late sodium current in rabbit ventricular myocytes.
- Source :
-
Experimental Physiology . Apr2015, Vol. 100 Issue 4, p399-409. 11p. - Publication Year :
- 2015
-
Abstract
- New Findings What is the central question of this study? What are the effects of protein kinase C (PKC) and Ca2+-calmodulin-dependent protein kinase II (CaMKII) on late sodium current ( INaL), reverse Na+-Ca2+ exchange current (reverse INCX) or intracellular Ca2+ 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 INaL and reverse INCX, and these effects may contribute to the effect of the glycoside to increase Ca2+ 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 ( INaL), as well as the diastolic intracellular calcium concentration and contractile shortening. Whether an increase of INaL participates in a pathway that can mediate the positive inotropic response to ouabain is unknown. We therefore determined the effects of ouabain on INaL, reverse Na+-Ca2+ exchange current (reverse INCX), intracellular Ca2+ ([Ca2+]i) levels and contractile shortening in rabbit isolated ventricular myocytes. Ouabain (0.1-8 μ m) markedly increased INaL and reverse INCX 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 INaL inhibitors TTX and ranolazine, the protein kinase C inhibitor bisindolylmaleimide and the Ca2+-calmodulin-dependent protein kinase II inhibitor KN-93. The enhancement by 0.5 μ m ouabain of ventricular myocyte contractility and intracellular Ca2+ 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 INaL and reverse INCX, and these effects may contribute to the effect of the glycoside to increase Ca2+ transients and contractility. Both protein kinase C and Ca2+-calmodulin-dependent protein kinase II activities may mediate or modulate these processes. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PROTEIN kinase C
*PROTEIN kinases
*OUABAIN
*GLYCOSIDES
*MUSCLE cells
Subjects
Details
- Language :
- English
- ISSN :
- 09580670
- Volume :
- 100
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Experimental Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 101853696
- Full Text :
- https://doi.org/10.1113/expphysiol.2014.083972