POSTNATAL DEVELOPMENT OF CALCIUM (Ca) RELEASE FROM CARDIAC SARCOPLASMIC RETICULUM(SR)

Abstract

Potentiation of contractile force of the first stimulated contraction following a rest interval (rest potentiation; RP)has been attributed to enhanced SR Ca release. Postnatal development of SR Ca release was assessed by evaluating RP in oxygenated left atrial strips isolated from immature (I;14-21 day old; n=11) and adult (A; n=9) rabbits. Isometric developed tension (DT) and dT/dt (pH=7.4;@30°C) were determined while pacing at 1 Hz (control) and following 2-90 sec. rest intervals (RI). RP was maximal at 60 sec. RI. Ryanodine (10−8M), a putative blocker of SR Ca release, abolished RP in both age groups. At 2.5mM extracellular Ca (Ca)e, DT was potentiated 176% in I and 287% in A while dT/dt was potentiated 163% in I and 295% in A (A>I; p<0.05). However, at 5mM (Ca)e, DT was potentiated 310% in I but only 215% in A(I>A;p<0.05). Mechanisms whereby the increase in (Ca)e increased RP in I might include either an increase in the action potential-mediated Ca influx that triggers SR Ca release or an increase in SR Ca loading. To evaluate these mechanisms, (Ca)e was increased from 2.5 to 5mM during the RI. RP was increased comparably in both age-groups, although the increase was small (≤25%) when compared with the 176% increase in RP in I when (Ca)e was increased to 5mM prior to RI. These results indicate that the immature heart requires a higher (Ca)e to optimize SR Ca loading as compared to the adult, and this difference may be a functional correlate of the recognized morphologic maturation of cardiac SR during postnatal development.