Sarcolemmal Ca2+-ATPase ability to transport Ca2+ gradually diminishes after myocardial infarction in the rat

• Published in: Cardiovascular research Vol. 81; no. 3; pp. 546 - 554
• Main Authors: Mackiewicz, Urszula, Maczewski, Michał, Konior, Anna, Tellez, James O., Nowis, Dominika, Dobrzynski, Halina, Boyett, Mark R., Lewartowski, Bohdan
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15-02-2009
• Subjects: Animals; Biological and medical sciences; Caffeine - pharmacology; Calcium - metabolism; Calcium handling; Calcium Signaling - drug effects; Cardiology. Vascular system; Coronary heart disease; Disease Models, Animal; Down-Regulation; Electric Stimulation; Heart; Heart remodelling; Male; Medical sciences; Myocardial Contraction; Myocardial infarction; Myocardial Infarction - enzymology; Myocardial Infarction - physiopathology; Myocarditis. Cardiomyopathies; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - enzymology; Plasma Membrane Calcium-Transporting ATPases - metabolism; Rats; Rats, Inbred WKY; RNA, Messenger - metabolism; Sarcolemmal Ca2+-ATPase; Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism; Sodium-Calcium Exchanger - metabolism; Time Factors; Ventricular Remodeling; Myocardial infarction; Sarcolemmal Ca; Heart remodelling; Calcium handling; ATPase; Heart; Calcium; Rat; Enzyme; Rodentia; Adenosinetriphosphatase; Cardiovascular disease; Coronary heart disease; Myocardial disease; Phlebology; Vertebrata; Mammalia; Animal; Sarcolemmal Ca2+-ATPase; Hydrolases; Circulatory system; Cardiology; Transport
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvn285

Aims Plasmalemmal Ca2+-ATPase (PMCA) is involved in Ca2+ handling and the regulation of intracellular signalling pathways in the heart. However, there is no information on its functioning in heart hypertrophy and failure. We aimed to investigate the Ca2+-transporting ability of PMCA, Na+/Ca2+ exchanger (NCX), and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), as well as the amplitude of Ca2+ transients and cell shortening in myocytes isolated from rat hearts at various time intervals after myocardial infarction (MI). Methods and results The rate of Ca2+ transport by PMCA, NCX, and SERCA2a was estimated from the rate constants of decay of electrically and caffeine-evoked Ca2+ transients in left ventricular myocytes isolated 1 week, 1 month, and 3 months after MI. One week, 1 month, and 3 months after MI, the transporting function of PMCA decreased by 27, 41, and 67%, respectively, compared with that in time-matched sham animals. This was accompanied by increased amplitude of Ca2+ transients, cell shortening, and SR Ca2+ content. Carboxyeosin, a blocker of PMCA, increased the amplitude of shortening in cells extracted from control hearts. This effect was absent 1 and 3 months after MI. PMCA1, 2, and 4 mRNAs were unchanged in the ventricular muscle 3 months after MI when compared with time-matched sham animals. The transporting function of NCX was increased by 65% only 3 months after MI, whereas that of SERCA2a was decreased by ∼18% at all three time points after MI. Conclusion The ability of PMCA to transport Ca2+ progressively decreases over 3 months after MI. This decrease may contribute to the increase in amplitude of Ca2+ transients and myocyte shortening.