Contribution of the sodium-calcium exchanger to contractions in immature rabbit ventricular myocytes

In immature cardiac myocytes, the sarcoplasmic reticulum is sparse. Thus, we hypothesized that sarcolemmal Ca₂+ influx through Na⁺-Ca²⁺ exchange is the dominant mechanism for modulating intracellular Ca²⁺ during contractions in fetal and neonatal hearts. We measured Na⁺ -Ca²⁺ exchange currents in neonatal and adult rabbit ventricular cells using a rapid solution switch into 0 mM external Na⁺. The current densities (mean ± SEM) were larger in 8 neonatal cells than in 10 adult cells (5.4 ± 1.38 versus 1.65 ± 0.25 pA/pF). Intracellular Ca²⁺ transients after inhibiting the sarcoplasmic reticulum with ryanodine and thapsigargin were unchanged in 15 neonatal cells, but decreased in 15 adult cells to 78.9 ± 5.6% of baseline. When the Ca²⁺ channels were also inhibited by adding nifedipine, Ca²⁺ transients from Na⁺-Ca²⁺ exchange were 30.0 ± 3.5% of baseline in neonatal cells compared with 13.4 ± 3.4% in adult cells. Simultaneous contractions were a larger percent of baseline in neonatal cells (85.7.6 ± 6.4%) than in adult cells (78.9 ± 5.6%) after inhibiting the sarcoplasmic reticulum, and were unmeasurable in many cells from both age groups after inhibiting the Ca²⁺ channels as well. The ratio of Na⁺ -Ca²⁺ exchanger mRNA to sarcoplasmic reticulum Ca²⁺-ATPase mRNA levels decreased from 1.0) ± 0.13 to 0.4 ± 0.03 to 0.26 ± 0.02 in fetal, neonatal and adult ventricles, respectively. These measurements were consistent with a dominant role for the Na⁺-Ca²⁺ exchanger in the immature heart.