| Autor: |
Dirkx, Ellen, Cazorla, Olivier, Schwenk, Robert W., Lorenzen-Schmidt, Ilka, Sadayappan, Sakthivel, Van Lint, Johan, Carrier, Lucie, van Eys, Guillaume J. J. M., Glatz, Jan F. C., Luiken, Joost J. F. P. |
| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Aug2012, Vol. 303 Issue 3, pH323-H331, 9p |
| Abstrakt: |
Cardiac myosin-binding protein C (cMyBP-C) is involved in the regulation of cardiac myofilament contraction. Recent evidence showed that protein kinase D (PKD) is one of the kinases that phosphorylate cMyBP-C. However, the mechanism by which PKD-induced cMyBP-C phosphorylation affects cardiac contractile responses is not known. Using immunoprecipitation, we showed that, in contracting cardiomyocytes, PKD binds to cMyBP-C and phosphorylates it at Ser315. The effect of PKD-mediated phosphorylation of cMyBP-C on cardiac myofilament function was investigated in permeabilized ventricular myocytes, isolated from wild-type (WT) and from cMyBP-C knockout (KO) mice, incubated in the presence of full-length active PKD. In WT myocytes, PKD increased both myofilament Ca2+ sensitivity (pCa50) and maximal Ca2+-activated tension of contraction (Tmax). In cMyBP-C KO skinned myocytes, PKD increased pCa50 but did not alter Tmax. This suggests that cMyBP-C is not involved in PKDmediated sensitization of myofilaments to Ca2+ but is essential for PKD-induced increase in Tmax. Furthermore, the phosphorylation of both PKD-Ser916 and cMyBP-C-Ser315 was contraction frequencydependent, suggesting that PKD-mediated cMyBP-C phosphorylation is operational primarily during periods of increased contractile activity. Thus, during high contraction frequency, PKD facilitates contraction of cardiomyocytes by increasing Ca2+ sensitivity and by an increased Tmax through phosphorylation of cMyBP-C. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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