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

Abstract

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.

• Authors: A Yao, Z Su, A Nonaka, I Zubair, K W Spitzer, J H Bridge, G Muelheims, J Ross Jr, W H Barry
• Journal: The American journal of physiology (Am J Physiol) Vol. 275 Issue 4 Pg. H1441-8 (10 1998) ISSN: 0002-9513 [Print] United States
• PMID: 9746495 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcium Channels
• Calcium Channels, L-Type
• Sodium-Calcium Exchanger
• Sodium
• Calcium-Transporting ATPases
• Calcium

Topics

• Animals
• Blood Pressure
• Body Weight
• Calcium (metabolism)
• Calcium Channels (physiology)
• Calcium Channels, L-Type
• Calcium-Transporting ATPases (metabolism)
• Cells, Cultured
• Heart (physiology, physiopathology)
• Heart Failure (etiology, metabolism, physiopathology)
• Homeostasis
• Kinetics
• Myocardium (metabolism)
• Organ Size
• Pacemaker, Artificial
• Patch-Clamp Techniques
• Rabbits
• Reference Values
• Sarcoplasmic Reticulum (enzymology)
• Sodium (metabolism)
• Sodium-Calcium Exchanger (physiology)