Excitation-contraction coupling in developing mammalian myocardium: evidence from voltage clamp studies

The single sucrose gap voltage clamp technique was used to study excitation-contraction coupling processes in right ventricular papillary muscles from New Zealand White rabbits at various stages of development. In response to voltage clamp controlled depolarizations, muscles from newborn rabbits were found to exhibit a monotonically increasing tension response reaching a steady state level that was maintained for the duration of depolarization. In contrast, more mature myocardium responded to similar depolarizations by developing an early peak of tension before relaxing to a steady state level. Measurement of the ratio of early peak or phasic tension to steady state or tonic tension revealed a statistically significant increase in the phasic tension component with maturation. In addition, Ca2+ loading of immature myocytes via a conditioning voltage clamp step resulted in enhancement of phasic tension in subsequent test depolarizations. Finally, the voltage dependence of tonic tension was found to be the same in all age groups. In contrast, the voltage dependence of phasic tension, seen only in the more mature myocardium, differed from that of tonic tension. The results of this investigation suggest that tension development in the immature myocardium is supported largely by the influx of Ca2+ across the sarcolemma. As the myocardium matures, intracellular Ca2+ uptake and rerelease by the sarcoplasmic reticulum plays an increasingly important role in tension development. A developmental schema is presented to account for the observed maturational changes in excitation-contraction coupling.