Yao A, Su Z, Nonaka A, Zubair I, Spitzer K W, Bridge J H, Muelheims G, Ross J, Barry W H
Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Am J Physiol. 1998 Oct;275(4):H1441-8. doi: 10.1152/ajpheart.1998.275.4.H1441.
To determine whether there are abnormalities in myocyte excitation-contraction coupling and intracellular Ca2+ concentration ([Ca2+]i) homeostasis in pacing-induced heart failure (PF), we measured L-type Ca2+ current (ICa,L) and Na+/Ca2+ exchanger current (INa/Ca) with voltage clamp and measured intracellular Na+ concentration ([Na+]i) and [Ca2+]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 [Ca2+]i transients (0.25 Hz, extracellular Ca2+ concentration = 1.08 mM) were significantly less in PF myocytes. Also, there was prolongation of the times to peak and decline of [Ca2+]i transients. ICa,L density was markedly decreased in PF myocytes. INa/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+/Ca2+ exchanger is impaired in these myocytes. In PF myocytes the decline of the [Ca2+]i transient when the Na+/Ca2+ exchanger was abruptly disabled was markedly prolonged compared with the decline in control myocytes, consistent with depressed sarcoplasmic reticulum (SR) Ca2+-ATPase function. RNase protection assay showed decreased levels of Na+/Ca2+ exchanger and SR Ca2+-ATPase mRNA in PF hearts, consistent with the function studies. We conclude that the functions of L-type Ca2+ channels, Na+/Ca2+ exchanger, and SR Ca2+-ATPase are impaired in myocytes from rabbit hearts with failure induced by rapid pacing. These abnormalities result in reduced [Ca2+]i transients and systolic and diastolic dysfunction and appear to account for the abnormal ventricular function observed.
为了确定在起搏诱导的心力衰竭（PF）中，心肌细胞兴奋 - 收缩偶联及细胞内钙离子浓度（[Ca2+]i）稳态是否存在异常，我们使用电压钳测量了L型钙电流（ICa,L）和钠钙交换电流（INa/Ca），并使用钠结合苯并呋喃异酞酸酯（SBFI）和氟钙红素3测量了从对照兔和起搏兔分离的心室肌细胞中的细胞内钠离子浓度（[Na+]i）和[Ca2+]i。PF心肌细胞中，电刺激的[Ca2+]i瞬变（0.25 Hz，细胞外钙离子浓度 = 1.08 mM）的收缩期和舒张期峰值水平及幅度显著降低。此外，[Ca2+]i瞬变达到峰值和下降的时间延长。PF心肌细胞中的ICa,L密度明显降低。使用快速溶液切换器快速暴露于0 Na+溶液时，在 -40 mV下诱导的PF心肌细胞中的INa/Ca显著降低，表明这些心肌细胞中钠钙交换器的功能受损。与对照心肌细胞中的下降相比，当钠钙交换器突然失活时，PF心肌细胞中[Ca2+]i瞬变的下降明显延长，这与肌浆网（SR）Ca2+ - ATP酶功能降低一致。核糖核酸酶保护试验显示PF心脏中钠钙交换器和SR Ca2+ - ATP酶mRNA水平降低，与功能研究结果一致。我们得出结论，快速起搏诱导的兔心力衰竭心肌细胞中，L型钙通道、钠钙交换器和SR Ca2+ - ATP酶的功能受损。这些异常导致[Ca2+]i瞬变减少以及收缩和舒张功能障碍，似乎是观察到的心室功能异常的原因。
