Abnormal myocyte Ca2+ homeostasis in rabbits with pacing-induced heart failure

• Published in: American journal of physiology. Heart and circulatory physiology 1998-10, Vol.275 (4), p.H1441
• Main Authors: Yao, Atsushi, Su, Zhi, Nonaka, Akihiko, Zubair, Iram, Spitzer, Kenneth W, Bridge, John H. B, Muelheims, Gerhard, Ross, John, Jr, Barry, William H
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.4.H1441

1  Division of Cardiology and 2  Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah Health Sciences Center, Salt Lake City, Utah 84132; and 3  Cardiology Division, University of California, San Diego, California 92093 To determine whether there are abnormalities in myocyte excitation-contraction coupling and intracellular Ca 2+ concentration ([Ca 2+ ] i ) homeostasis in pacing-induced heart failure (PF), we measured L-type Ca 2+ current ( I Ca,L ) and Na + /Ca 2+ exchanger current ( I Na/Ca ) with voltage clamp and measured intracellular Na + concentration ([Na + ] i ) and [Ca 2+ ] i with the use of sodium-binding benzofuran isophthalate (SBFI) and fluo 3 in ventricular myocytes isolated from control and paced rabbits. The peak systolic and diastolic levels and the amplitude of electrically stimulated [Ca 2+ ] i transients (0.25 Hz, extracellular Ca 2+ concentration = 1.08 mM) were significantly less in PF myocytes. Also, there was prolongation of the times to peak and decline of [Ca 2+ ] i transients. I Ca,L density was markedly decreased in PF myocytes. I Na/Ca at 40 mV elicited by rapid exposure to 0 Na + solution with a rapid solution switcher was significantly reduced in PF myocytes, suggesting that the function of the Na + /Ca 2+ exchanger is impaired in these myocytes. In PF myocytes the decline of the [Ca 2+ ] i transient when the Na + /Ca 2+ exchanger was abruptly disabled was markedly prolonged compared with the decline in control myocytes, consistent with depressed sarcoplasmic reticulum (SR) Ca 2+ -ATPase function. RNase protection assay showed decreased levels of Na + /Ca 2+ exchanger and SR Ca 2+ -ATPase mRNA in PF hearts, consistent with the function studies. We conclude that the functions of L-type Ca 2+ channels, Na + /Ca 2+ exchanger, and SR Ca 2+ -ATPase are impaired in myocytes from rabbit hearts with failure induced by rapid pacing. These abnormalities result in reduced [Ca 2+ ] i transients and systolic and diastolic dysfunction and appear to account for the abnormal ventricular function observed. isolated myocyte; calcium transient; calcium channel; sodium/calcium exchanger; sarcoplasmic reticulum calcium adenosine 5'-triphosphatase