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.

Research progress on the activation mechanism of NLRP3 inflammasome in septic cardiomyopathy

“…Inflammatory cascade response can produce myocardial contractile disorders through calcium response 64,65 . As a second messenger, calcium ions also play an important role in oxidative stress, inflammatory response, and mitochondrial dysfunction that occur in SCM 66 .…”

“…Inflammatory cascade response can produce myocardial contractile disorders through calcium response. 64 , 65 As a second messenger, calcium ions also play an important role in oxidative stress, inflammatory response, and mitochondrial dysfunction that occur in SCM. 66 Ca 2+ activation and some metabolic changes are upstream signals of NLRP3 activation, and these pathways are interconnected with each other.…”

Does Myocardial Atrophy Represent Anti-Arrhythmic Phenotype?

“…Moreover, the inhibition of Ca 2+ handling due to hypocaloric feeding has been reported [ 63 ], which may prevent Ca 2+ -overload-induced arrhythmias [ 120 ]. On the other hand, trans-sarcolemmal Ca 2+ fluxes were increased in the cardiac atrophy of the unloaded heterotopically transplanted rat heart [ 121 , 122 ]. Moreover, Ca 2+ pump, Na + -Ca 2+ exchange and Ca 2+ -transient activities of cardiomyocytes affecting cardiac function were increased in early cardiac atrophy, suggesting an adaptive mechanism to maintain contractile function [ 123 ].…”

“…The disorientation and loss of contractile filaments, as well as loss of Z-line substance, were observed [ 1 ]. Interestingly, cardiomyocyte sarcolemma from unloaded transplanted had higher contents of phosphatidic acid, sphingomyelin, and cholesterol [ 122 ]. The progressive depletion of titin (which acts as a mechanosensor) leads to sarcomere disassembly, atrophy, and eventually, dilated cardiomyopathy [ 125 ].…”