Sarcolemmal Alterations in Unloaded Rat Heart after Heterotopic Transplantation

Abstract

AbstractFollowing heterotopic transplantation, the rat heart undergoes atrophy and exhibits delayed cardiac relaxation without any changes in contraction and systolic Ca2+ transients. Furthermore, the sarcoplasmic reticular Ca2+ uptake and release activities were reduced and Ca2+ influx through L-type Ca2+ channels was increased in the atrophied heart. Since Ca2+ movements at sarcolemma are intimately involved in the regulation of intracellular Ca2+ concentration, the present study was undertaken to test if sarcolemma plays any role to maintain cardiac function in the atrophied heart.The characteristics of sarcolemmal Ca2+ pump and Na+–Ca2+ exchange activities were examined in 8 weeks heterotopically isotransplanted rat hearts which did not support hemodynamic load and underwent atrophy. Sarcolemmal ATP (adenosine triphosphate)-dependent Ca2+ uptake and Ca2+-stimulated ATPase (adenosine triphosphatase) activities were increased without any changes in Na+–K+ ATPase activities in the transplanted hearts. Although no alterations in the Na+-dependent Ca2+ uptake were evident, Na+-induced Ca2+ release was increased in the transplanted heart sarcolemmal vesicles. The increase in Na+-induced Ca2+ release was observed at different times of incubation as well as at 5, 20, and 40 mM Na+. The sarcolemma from transplanted hearts also showed higher contents of phosphatidic acid, sphingomyelin, and cholesterol.These results indicate that increases in the sarcolemmal, Ca2+ transport activities in unloaded heart may provide an insight into adaptive mechanism to maintain normal contractile behavior of the atrophic heart.