Reciprocal changes in the postnatal expression of the sarcolemmal Na+-Ca2+-exchanger and SERCA2 in rat heart

The aim of this study was to examine the relationship between sarcolemmal Na+-Ca2+ exchangers and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) expression and the developmental differences in cardiac Ca2+ handling. Postnatal steady-state mRNA and protein levels were analysed in rat ventricular myocardium by Northern and immunoblot analysis, respectively. This was compared to Na+ gradient-induced and SR oxalate-supported Ca2+ transport in isolated membranes. Na+-Ca2+ exchanger mRNA declined by 75% between day 1 and 30, whereas SR Ca2+-ATPase mRNA levels increased by 97% during this period. The Na+-Ca2+ exchanger mRNA/Ca2+-ATPase mRNA ratio was found to be inversely related to postnatal age. The changes in mRNA levels were associated with corresponding developmental differences in the Ca2+ transport activities of the respective membrane proteins. In crude membranes, the Na+-dependent Ca2+ transport activity (at 75 μm Ca2+) declined gradually (P<0.01; mean±s.e.) from 17.7±2.4 nmoles Ca2+/g wet tissue/2s at day 1–3 (n=5) to a value of 4.2±1.1 at day 40 (n=4). Conversely, SR Ca2+ uptake increased (P<0.01) 2.6-fold during this period. The inversely related changes in the post-natal expression and function of the Na+-Ca2+ exchanger and SR Ca2+-ATPase suggest a coordinated control at the pretranslational level of the cellular Ca2+ transport processes mediated by the two membrane proteins.