Reduced Phospholamban Phosphorylation Is Associated With Impaired Relaxation in Left Ventricular Myocytes From Neuronal NO Synthase–Deficient Mice

• DOI: 10.1161/circresaha.107.164798
• Publication Date: 2007-11-16T02:30:15Z
• Authors: Yin Hua Zhang; Mei Hua Zhang; Claire E. Sears; Krzysztof Emanuel; Charles Redwood; Ali El-Armouche; Evangelia G. Kranias; Barbara Casadei
• Keywords: Phospholamban

Stimulation of nitric oxide (NO) release from the coronary endothelium facilitates myocardial relaxation via a cGMP-dependent reduction in myofilament Ca2+ sensitivity. Recent evidence suggests that NO released by neuronal synthase (nNOS) myocardium can also hasten left ventricular relaxation; however, mechanism underlying these findings is uncertain. Here we show both (TR50) and rate [Ca2+]i transient decay (tau) are significantly prolonged field-stimulated or voltage-clamped myocytes nNOS-/- mice wild-type (nNOS+/+) after acute nNOS inhibition. Disabling sarcoplasmic reticulum abolished differences TR50 tau, suggesting impaired reuptake may account for slower mice. In line with findings, disruption (but not endothelial NOS) decreased phospholamban phosphorylation (P-Ser16 PLN), whereas inhibition had no effect on tau PLN-/- myocytes. Inhibition cGMP signaling either group protein kinase A difference PLN decreasing P-Ser16 prolonging nNOS+/+ Conversely, type 1 2A phosphatases shortened increased but myocytes, agreement data showing phosphatase activity hearts. Taken together, our identify novel which promotes regulating A-mediated cGMP-independent activity.