Role of sarcoplasmic reticulum in the relaxant effect of increasing contraction frequency. Insights from mammalian and amphibian heart

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

La Plata, Argentina

Congreso; XI Meeting of the International Society for Heart Research; 2002

Latin American Section of the International Society for Heart Research

The positive inotropic effect of increasing contraction frequency (CF) is associated with a relaxant or positive lusitropic effect (PLE), the mechanism of which is poorly understood. Recent experiments associated this phenomenon with the increase in the phosphorylation of the Thr17 residue of phospholamban (PLB), the sarcoplasmic reticulum (SR) protein that regulates the SR Ca2+ pump (Hagemann et al, JBC, 2000). However, other experiments indicated that the PLE of increasing CF was not associated with any significant increase in PLB phosphorylation (Hussain et al, Am J Physiol, 1997). To gain further insight into the mechanism of the PLE of increasing CF, experiments were performed in cat papillary muscles and  isolated myocytes, and ventricular strips from the  toad (a species with poorly developed SR).The positive inotropic effect of increasing CF was associated with a PLE in both species. In papillary muscles the administration of ryanodine + thapsigargin (R+T) to functionally inhibit the SR , converted the PLE into a negative LE. In the isolated myocytes, the PLE (decrease in half relaxation time of the Ca2+ transient by 113.8±25.9 msec) was associated with an increase in Thr17 phosphorylation of PLB without significant changes in Ser16  phosphorylation. In the toad ventricle, the PLE of CF, was surprisingly diminished in the presence of R+T, but still present. The results indicate that in a mammalian species like the cat, the PLE of CF was strictly dependent on the SR and can at least partially be explained by Thr17 phosphorylation of PLB, whereas in the amphibian  ventricle other mechanisms different from the SR, seem to participate.