Sarcolemmal Alterations in Unloaded Rat Heart after Heterotopic Transplantation

Abstract

Following 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.

Keywords

cardiac contractility - sarcolemmal Ca²⁺ pump - sarcolemmal Na⁺–Ca²⁺ exchange - membrane phospholipids - cardiac atrophy - Ca²⁺ transport in myocardium - transplanted heart

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