The significance of phosphorylation of myosin light chains in heart

Pj, England

doi:10.1016/s0022-2828(84)80623-9

Cited by 22 publications

(2 citation statements)

References 12 publications

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“…These findings would suggest that, whereas the phosphorylation of Thr 17 participates in the recovery of contractile performance that follows the ischemic episode, the phosphorylation of Ser 16 is not involved. However, either inhibition of CaMKII or blockade of the ␤-adrenergic cascade may alter the phosphorylation of several proteins other than PLB (8,10,12,20,35,40), which might also influence the recovery of contraction after the ischemia and therefore mask the actual role of PLB residues.…”

Section: Resultsmentioning

confidence: 99%

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

Said¹,

Vittone²,

Mundiña‐Weilenmann³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Said, M., L. Vittone, C. Mundiñ a-Weilenmann, P. Ferrero, E. G. Kranias, and A. Mattiazzi. Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants. uptake and myocardial contractility and relaxation. In perfused rat hearts submitted to ischemia-reperfusion, we previously showed an ischemia-induced Ser 16 phosphorylation that was dependent on ␤-adrenergic stimulation and an ischemia and reperfusion-induced Thr 17 phosphorylation that was dependent on Ca 2ϩ influx. To elucidate the relationship between these two PLB phosphorylation sites and postischemic mechanical recovery, rat hearts were submitted to ischemiareperfusion in the absence and presence of the CaMKII inhibitor KN-93 (1 M) or the ␤-adrenergic blocker dl-propranolol (1 M). KN-93 diminished the reperfusion-induced Thr 17 phosphorylation and depressed the recovery of contraction and relaxation after ischemia. dl-Propranolol decreased the ischemia-induced Ser 16 phosphorylation but failed to modify the contractile recovery. To obtain further insights into the functional role of the two PLB phosphorylation sites in postischemic mechanical recovery, transgenic mice expressing wild-type PLB (PLB-WT) or PLB mutants in which either Thr 17 or Ser 16 were replaced by Ala (PLB-T17A and PLB-S16A, respectively) into the PLB-null background were used. Both PLB mutants showed a lower contractile recovery than PLB-WT. However, this recovery was significantly impaired all along reperfusion in PLB-T17A, whereas it was depressed only at the beginning of reperfusion in PLB-S16A. Moreover, the recovery of relaxation was delayed in PLB-T17A, whereas it did not change in PLB-S16A, compared with PLB-WT. These findings indicate that, although both PLB phosphorylation sites are involved in the mechanical recovery after ischemia, Thr 17 appears to play a major role. -ATPase 2 (SERCA2)] and/or in the rate of Ca 2ϩ reuptake by the SR have been described in several species, including rats, mice, dogs and humans, submitted to moderate and reversible injury during cardiac surgery (21,23,41,43). A decrease in the intracellular Ca 2ϩ transient has indeed been described in stunned myocytes isolated from chronically instrumented pigs (18) but was not detected in stunned rat myocytes and ventricular trabeculae or in isolated perfused ferret and dog hearts (5,9,11,18 appears to be normalized before complete recovery of myocardial performance in several species (5, 9, 11) does not necessarily mean that Ca 2ϩ homeostasis is not altered during ischemia and reperfusion. There is a compelling body of evidence that indicates that in all species studied, cytosolic Ca 2ϩ concentration rises during ischemia (2,27,31). Furthermore, reperfusion in-

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Section: Resultsmentioning

confidence: 99%

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

Said¹,

Vittone²,

Mundiña‐Weilenmann³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…First, the level of phosphorylation of myosin light chain 2 is not changed by /-adrenergic stimulation. 59 Second, the specific enzyme that phosphorylates myosin light chain 2, myosin light chain kinase, is activated by calcium, not cAMP.61 It is unlikely that the activity of this enzyme would be elevated under the condition of our experiment, since Ba2+ was used for activating the muscle to a constant level during contracture. After the addition of DcAMP or IBMX, or of adrenaline,3 there was no consistent change in contracture tension to suggest an elevation of Ca2+ or Ba2+ that might enhance myosin light chain kinase activity.…”

Section: Difference In Response Between V1 and V3 Heartsmentioning

confidence: 90%

Effects of dibutyryl cyclic AMP, ouabain, and xanthine derivatives on crossbridge kinetics in rat cardiac muscle.

Hoh

Rossmanith

Hamilton

1991

Circulation Research

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In a previous communication, we showed that beta-adrenergic stimulation of cardiac muscles was associated with an increase in the rate of cycling of crossbridges as measured by perturbation analysis in the frequency domain. In this analysis, the frequency at which dynamic stiffness is a minimum (fmin) is taken as a measure of the rate of crossbridge cycling. In this paper, we test the hypothesis that the beta-adrenergic receptor-induced increase in crossbridge cycling rate is mediated by elevation of the intracellular level of cyclic AMP. The approach taken is to compare the effects on fmin in rat papillary muscles during Ba(2+)-activated contractures of 1) an agonist of cyclic AMP that can easily penetrate the cell, namely, dibutyryl cyclic AMP, 2) agents that block cyclic AMP phosphodiesterase, namely, the xanthine derivatives isobutylmethylxanthine and caffeine, and 3) an inotropic agent that does not affect the intracellular level of cyclic AMP, namely, ouabain. Our results showed that dibutyryl cyclic AMP at a dose of 5 mM has the same actions as beta-adrenergic stimulation: it potentiated the isometric twitch force, reduced the time to peak tension and time to half relaxation, and shifted fmin by a factor of 1.8 +/- 0.1 (n = 5). Isobutylmethylxanthine at up to 1.1 mM also acted in the same manner, increasing fmin by a factor of 1.8 +/- 0.2 (n = 6), but ouabain, at a dose (0.03 mM) sufficient to potentiate twitch force by 40 +/- 2% (n = 4), was without effect on the time course of the twitch nor was fmin changed (n = 4). Our findings support the hypothesis that a beta-adrenergic receptor-mediated increase in crossbridge cycling rate is due to an increase in intracellular cyclic AMP level and illustrate the usefulness of the frequency domain analysis approach in the analysis of the mechanism of action of inotropic agents.

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Myofilaments: The End Effector of E-C Coupling

Bers¹

2001

Excitation-Contraction Coupling and Cardiac Contractile Force

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The significance of phosphorylation of myosin light chains in heart

Cited by 22 publications

References 12 publications

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

Effects of dibutyryl cyclic AMP, ouabain, and xanthine derivatives on crossbridge kinetics in rat cardiac muscle.

Myofilaments: The End Effector of E-C Coupling

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