The frequency-induced relaxant effect is mediated by a CaMKII independent pathway

PALOMEQUE J; VALVERDE CA; MUNDIÑA-WEILENMANN C; VILA-PETROFF M; MATTIAZZI A

Brisbane, Australia

Congreso; XVIII World Congress International Society for Heart Research; 2004

International Society for Heart Research

An increase in stimulation frequency (ISF) causes an acceleration of relaxation (FDAR). Several mechanisms have been postulated to explain this effect: a CaMKIIphosphorylation of Thr17 site of PLB (PThr17) and/or of Ser38 site of SERCA, or a CaMKII-independent mechanism, whereby ISF-induced Ca2+ elevation would disrupt the SERCA-PLB interaction.We examined these mechanisms in Indo-1-loaded isolated cat myocytes. The ISF significantly reduced time to half Ca2+ transient decay, (t1/2CaiT), and increased PThr17. Comparison of the time course of FDAR with the increase in PThr17, produced by ISF from 10 to 50 ppm, showed that the t1/2CaiT was maximally decreased after 2.5 s of ISF, whereas the increase in PThr17 became significant only after 15 s of ISF (Fig. 1). Additionally, the CaMKII-inhibitor KN-93, significantly decreased the PThr17 evoked by ISF, but failed to affect FDAR. The results World indicate that CaMKII-phosphorylation pathways are not envolved in FDAR in cat myocytes. More likely, a direct effect of the increase in Ca2+ on SERCA-PLB interaction, promoting its dissociation, would lead to an increase in SR Ca2+ uptake and myocardial relaxation.