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 unmeasureable in many cells from both age groups after inhibiting the Ca2+ channels as well. The ratio of Na(+)-Ca2+ exchanger mRNA to sarcoplasmic reticulum Ca(2+)-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.
Chin
T K
TK
Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City 84113, USA.
Christiansen
G A
GA
Caldwell
J G
JG
Thorburn
J
J
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D009200:Myocardial Contraction / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium; D019831:Sodium-Calcium Exchanger
D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium