SR Ca²⁺ refilling upon depletion and SR Ca²⁺ uptake rates during development in rabbit ventricular myocytes

Abstract

While it has been reported that a sparse sarcoplasmic reticulum (SR) and a low SR Ca2+ pump density exist at birth, we and others have recently shown that significant amounts of Ca2+ are stored in the neonatal rabbit heart SR. Here we try to determine developmental changes in SR Ca2+ loading mechanisms and Ca2+ pump efficacy in rabbit ventricular myocytes. SR Ca2+ loading (loadSR) and k0.5 (Ca2+ concentration at half-maximal SR Ca2+ uptake) were higher and lower, respectively, in younger age groups. Inhibition of the L-type calcium current ( ICa) with 15 μM nifedipine dramatically reduced loadSR in older but not in younger age groups. In contrast, subsequent inhibition of the Na+/Ca2+ exchanger (NCX) with 10 μM KB-R7943 strongly reduced loadSR in the younger but not the older age groups. Accordingly, the time integral of the inward NCX current (tail INCX) elicited on repolarization was highly sensitive to nifedipine in the older groups and sensitive to KB-R7943 in the younger groups. Interestingly, slow SR loading took place in the presence of both nifedipine and KB-R7943 in all age groups, although it was less prominent in the older groups. We conclude that the SR loading capacity at the earliest postnatal stages is at least as large as that of adult myocytes. However, reverse-mode NCX plays a prominent role in SR Ca2+ loading at early postnatal stages while ICa is the main source of SR Ca2+ loading at late postnatal and adult stages.

Calcium handling in zebrafish ventricular myocytes

“…Importantly, our findings show a considerably larger I Ca,L density in the zebrafish than in mammalian and human cardiomyocytes, making a substantial contribution of SR calcium release to the intracellular calcium transient less likely and thus complicating the study of the rapidly increasing number of mutations linked to defective SR function and calcium handling (10, 13, 28, 29, 31, 36, 40, 46, 47). Similarly, the observed plateau in calcium Another complicating factor is the extensive use of embryonic zebrafish hearts for screening purposes, as there are known differences in morphological, electrophysiological, and functional features of embryonic, neonatal, and adult cardiomyocytes (23)(24)(25)(26). Specifically, our laboratory has documented several differences in intracellular calcium handling among neonatal and adult ventricular myocytes.…”

Detection, Properties, and Frequency of Local Calcium Release from the Sarcoplasmic Reticulum in Teleost Cardiomyocytes

“…Morphologically, both are slim and elongated and lack t-tubules [20], [41], [42]. The SR also has about 3-fold higher calcium storing capacity in neonatal than adult rabbit ventricular myocytes [43], and reverse mode Na + -Ca 2+ exchange has been shown to play a prominent role in both trout [15], [16] and neonatal cardiomyocytes [44], [45].…”