Ca2+-calmodulin-dependent protein kinase phosphorylation of ryanodine receptor may contribute to the beta-adrenergic regulation of myocardial contractility independently of increases in heart rate.

MATTIAZZI A; VITTONE L; MUNDIÑA-WEILENMANN C

CIRCULATION RESEARCH

Lippincott Williams & Wilkins

Año: 2008 vol. 103 p. 10 - 11

0009-7330

The purpose of our letter is 1. To point out an omission of the authors in their discussion, which might lead to the erroneous acceptance that Ser2808/09 is the only RyR2 site by which isoproterenol can alter the function of the SR Ca2+ release channel. The authors exclude –without experimental support- any possible participation of isoproterenol-induced RyR2 phosphorylation different from Ser2808/9 site in the positive inotropic effect of isoproterenol. We demonstrated in a previous work  that CaMKII-dependent phosphorylation of the RyR2 at Ser2815 site was responsible for the â-adrenergic-induced increase in the channel activity. 2.To indicate that we disagree with a concept that MacDonnell et al put forward in their discussion, which suggests that the only mechanism by which isoproterenol may produce an increase in CaMKII activation is by increasing heart rate. Evidence has grown supporting a critical role of CaMKII in the effects induced by both acute and chronic â-adrenoceptor stimulation. These effects however occur without the requisite of a â-adrenergic-induced increase in heart rate.