Enhanced Ca2+-Activated Na+-Ca2+Exchange Activity in Canine Pacing-Induced Heart Failure
作者:
Ion Hobai,
Brian O’Rourke,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2000)
卷期:
Volume 87,
issue 8
页码: 690-698
ISSN:0009-7330
年代: 2000
出版商: OVID
关键词: Na+-Ca2+exchange;heart failure;tachycardia
数据来源: OVID
摘要:
Defective excitation-contraction coupling in heart failure is generally associated with both a reduction in sarcoplasmic reticulum (SR) Ca2+uptake and a greater dependence on transsarcolemmal Na+-Ca2+exchange (NCX) for Ca2+removal. Although a relative increase in NCX is expected when SR function is impaired, few and contradictory studies have addressed whether there is an absolute increase in NCX activity. The present study examines in detail NCX density and function in left ventricular midmyocardial myocytes isolated from normal or tachycardic pacing–induced failing canine hearts. No change of NCX current density was evident in myocytes from failing hearts when intracellular Ca2+([Ca2+]i) was buffered to 200 nmol/L. However, when [Ca2+]iwas minimally buffered with 50 &mgr;mol/L indo-1, Ca2+extrusion via NCX during caffeine application was doubled in failing versus normal cells. In other voltage-clamp experiments in which SR uptake was blocked with thapsigargin, both reverse-mode and forward-mode NCX currents and Ca2+transport were increased >2-fold in failing cells. These results suggest that, in addition to a relative increase in NCX function as a consequence of defective SR Ca2+uptake, there is an absolute increase in NCX function that depends on [Ca2+]iin the failing heart.
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