Developmental changes in the contributions of the Ca²⁺ channels and Na⁺-Ca2⁺ exchanger to contractions in rabbit cardiac ventricular myocytes

Sarcolemmal Ca2influx is considered more important for contractions in immature vs mature hearts. To measure developmental changes in the contributions of the Ca²⁺ channels and ²⁺-Ca²⁺ exchanger to contractions, intracellular Ca2transients were measured in field-stimulated ventricular myocytes from 1 -4 day neonatal and 4-6 week adult New Zealand White Rabbits at 24° C. The cells were loaded for 10 minutes with 10 uM indo-1 AM, and washed in normal Tyrode's solution before study. After inhibiting the sarcoplasmic reticulum (SR) with 500 nM thapsigargin and 10 pM ryanodine, Ca²⁺ transients were unchanged in 22 neonatal cells, but decreased in 20 adult cells to 88.8+3.4% of baseline (mean+SEM, P<0.01). With the SR_and .Ca²⁺_channejs inhibited (thapsigargin, ryanodine + 20 uM nifedipine), Ca²⁺ transients from reverse ²⁺-Ca²⁺ exchange were larger in 5 neonatal compared to 7 adult cells (61 4+0.7% vs. 11.6+4.9%, P<0 001). With the SRCa2" channels and ²⁺-Ca²⁺ exchanger inhibited (thapsigargin, ryanodine + 5 mM Ni²⁺), Ca²⁺ transients were eliminated in cells from both age groups. In conclusion, the ²⁺-Ca²⁺ exchanger is responsible during contractions for =60% of the rise in intracellular Ca²⁺ in neonatal vs. = 12% of the rise in adult rabbit myocytes The relative contribution of the Ca²⁺ channels vs. ²⁺-Ca²⁺ exchanger is smaller in the neonatal cells, but 6-fold larger in the adult cells.