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Updated: Feb 2, 2026
Modified Heterotopic Abdominal Heart Transplantation and a Novel Aortic Regurgitation Model in Rats
Published on: June 2, 2023
Sarcolemmal Alterations in Unloaded Rat Heart after Heterotopic Transplantation
Naoki Makino1, Paul Ganguly2, Vijayan Elimban3
1Department of Molecular and Clinical Gerontology, Medical Institute of the Bioregulation, Kyushu University, Oita, Japan.
Insights
In unloaded, atrophied rat hearts, sarcolemmal Ca2+ transport increased. This adaptive mechanism helps maintain normal heart contraction despite reduced sarcoplasmic reticulum function.
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
- Biochemistry
Background:
- Heterotopic heart transplantation leads to cardiac atrophy and delayed relaxation.
- Sarcoplasmic reticulum Ca2+ handling is altered in atrophied hearts, with reduced uptake/release and increased L-type Ca2+ channel influx.
- Sarcolemmal Ca2+ movements are critical for intracellular Ca2+ regulation.
Purpose of the Study:
- To investigate the role of sarcolemma in maintaining cardiac function in atrophied hearts.
- To examine sarcolemmal Ca2+ pump and Na+-Ca2+ exchange activities in unloaded, transplanted rat hearts.
Main Methods:
- Analysis of sarcolemmal Ca2+ pump and Na+-Ca2+ exchange activities in 8-week heterotopically isotransplanted rat hearts.
- Measurement of sarcolemmal ATP-dependent Ca2+ uptake, Ca2+-stimulated ATPase, and Na+-K+ ATPase activities.
- Assessment of Na+-dependent Ca2+ uptake and Na+-induced Ca2+ release in sarcolemmal vesicles.
- Quantification of sarcolemmal lipid content (phosphatidic acid, sphingomyelin, cholesterol).
Main Results:
- Transplanted hearts showed increased sarcolemmal ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activity.
- Na+-K+ ATPase activity remained unchanged.
- Na+-dependent Ca2+ uptake was unaltered, but Na+-induced Ca2+ release was significantly increased.
- Sarcolemma from transplanted hearts exhibited higher levels of phosphatidic acid, sphingomyelin, and cholesterol.
Conclusions:
- Increased sarcolemmal Ca2+ transport activities in unloaded hearts may represent an adaptive mechanism.
- These adaptations help preserve normal contractile function in the atrophic heart.
- Sarcolemmal lipid composition changes may contribute to altered Ca2+ transport.
Abstract:
Following heterotopic transplantation, the rat heart undergoes atrophy and exhibits delayed cardiac relaxation without any changes in contraction and systolic Ca 2+ transients. Furthermore, the sarcoplasmic reticular Ca 2+ uptake and release activities were reduced and Ca 2+ influx through L-type Ca 2+ channels was increased in the atrophied heart. Since Ca 2+ movements at sarcolemma are intimately involved in the regulation of intracellular Ca 2+ 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 Ca 2+ pump and Na + -Ca 2+ 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 Ca 2+ uptake and Ca 2+ -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 Ca 2+ uptake were evident, Na + -induced Ca 2+ release was increased in the transplanted heart sarcolemmal vesicles. The increase in Na + -induced Ca 2+ 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, Ca 2+ transport activities in unloaded heart may provide an insight into adaptive mechanism to maintain normal contractile behavior of the atrophic heart.
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