Postnatal Development of Calcium Channels in Cardiac Muscle

Abstract

During the postnatal period, excitation-contraction coupling changes dramatically in rat ventricular muscle, as evidenced by modifications in the sensitivity of systolic contraction to external Ca²⁺ (1) and to modulators of Ca²⁺ channels (2,3). The potency of L-channel blockers (nifedipine, verapamil) as inhibitors of systolic contraction is lower in adult than in neonatal ventricle and conversely, the negative inotropic effect of ryanodine, a selective modulator of sarcoplasmic reticulum (SR) Ca²⁺ release channels, is more pronounced in adult than in neonatal tissue. These findings suggest that, in neonatal ventricle, most of the Ca²⁺ that is needed to activate the myofilaments originates from the extracellular milieu, whereas, in adult tissue, the SR Ca²⁺ stores become progressively more important as a source of activator Ca²⁺. These functional changes are parallelled by marked ultrastructural modifications. In particular, the volume percentage of SR increases 2-fold in the early postnatal period and the transverse tubular system, which is not detectable at birth, develops over the first postnatal weeks (4). In view of the different response of neonatal and adult heart to L-channel blockers and ryanodine, we decided to compare the properties of their respective receptors in cardiac membranes isolated at various ages, using [³H]( + )-PN200-110 ([³H]-isradipine) and [³H]ryanodine to label sarcolemmal dihydropyridine-sensitive Ca²⁺ channels and SR ryanodine-sensitive Ca²⁺ channels, respectively.