Maturational changes in excitation-contraction coupling in mammalian myocardium

The single sucrose gap voltage clamp technique has been used to study the relation between membrane electrical activity and tension generation in right ventricular papillary muscles from New Zealand White rabbits at various stages of development. In response to voltage clamp-controlled depolarization, muscles from newborn rabbits develop monotonically increasing tension that reaches a steady state level, whereas more mature myocardium responds to similar depolarization by developing an early peak of tension before relaxing to a steady state level. The ratio of early peak or phasic tension to steady state or tonic tension increases significantly with maturation. Calcium (Ca2+) loading of immature myocytes enhances phasic tension in a subsequent test depolarization. Although the voltage dependence of tonic tension increases monotonically in all age groups, phasic tension, seen only in the more mature myocardium, displays a "bell-shaped" dependence on voltage. Addition of ryanodine, known to interfere with Ca2+ release from the sarcoplasmic reticulum, markedly reduces the phasic component of tension in mature myocardium, and the voltage clamp-induced tension in the adult closely resembles that of the normal newborn. These results suggest that tension development in immature myocardium is supported largely by the influx of Ca2+ across the sarcolemma. As the myocardium matures, the sarcoplasmic reticulum plays an increasingly important role in tension generation. A developmental schema is presented to account for the observed maturational changes in excitation-contraction coupling. The clinical implications of these changes are discussed as they relate to the practice of pediatric cardiology.