Developmental differences in the response of cytosolic free calcium to potassium depolarization and cardioplegia in cardiac myocytes.
Several biochemical and functional characteristics of immature myocardium suggest a diminished capacity to regulate intracellular Ca2+ during stress. In particular, cellular calcium overload has been postulated as an important pathogenetic mechanism accounting for suboptimal functional recovery following cardioplegia in immature myocardium. Using intracellular Fura-2 fluorescence as Ca2+ indicator, we measured cytosolic free calcium ([Cai]) in single myocytes and cell suspensions derived from both juvenile (4 weeks post-partum) and mature (6-12 months post-partum) New Zealand white rabbits. Resting [Cai] in juvenile heart cells (26 +/- 3 nM) were approximately 50% of that found in adult myocytes (55 +/- 5 nM). In addition, on exposure to increasing concentrations of extracellular potassium ([Kex]), adult but not juvenile myocytes exhibited increases in [Cai]. These two observations underscore developmental differences in intracellular Ca2+ homeostasis. Of particular clinical relevance is the [Cai] response to cardioplegia containing 16 mM [Kex]: neither group demonstrated the expected [Cai] increase in response to potassium depolarization. The lack of [Cai] response to cardioplegia was most likely due to the high levels of Mg2+ (32 mM) contained in cardioplegic solutions. We conclude that cellular calcium overload does not occur following exposure to cardioplegia alone. Accordingly, these findings do not account for recognized developmental differences in functional recovery from "myocardial protection".
Cyran
S E
SE
Department of Pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Ditty
S E
SE
Baylen
B G
BG
Cheung
J
J
LaNoue
K F
KF
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D003600:Cytosol; D016257:Fura-2 / Q000378:metabolism; D006321:Heart / Q000254:growth & development*; D006324:Heart Arrest, Induced; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D011817:Rabbits
D008274:Magnesium; D011188:Potassium; D002118:Calcium; D016257:Fura-2