Effects of Na(+)/Ca(2+) exchanger downregulation on contractility and [Ca(2+)](i) transients in adult rat myocytes |
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Authors: | Tadros George M Zhang Xue-Qian Song Jianliang Carl Lois L Rothblum Lawrence I Tian Qiang Dunn Jeremy Lytton Jonathan Cheung Joseph Y |
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Institution: | Department of Medicine, Geisinger Medical Center, Danville, Pennsylvania 17822, USA. |
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Abstract: | Postmyocardial infarction (MI) rat myocytes demonstrated depressed Na(+)/Ca(2+) exchange (NCX1) activity, altered contractility, and intracellular Ca(2+) concentration (Ca(2+)](i)) transients. We investigated whether NCX1 downregulation in normal myocytes resulted in contractility changes observed in MI myocytes. Myocytes infected with adenovirus expressing antisense (AS) oligonucleotides to NCX1 had 30% less NCX1 at 3 days and 66% less NCX1 at 6 days. The half-time of relaxation from caffeine-induced contracture was twice as long in ASNCX1 myocytes. Sarcoplasmic reticulum (SR) Ca(2+)-ATPase abundance, SR Ca(2+) uptake, resting membrane potential, action potential amplitude and duration, L-type Ca(2+) current density and cell size were not affected by ASNCX1 treatment. At extracellular Ca(2+) concentration (Ca(2+)](o)) of 5 mM, ASNCX1 myocytes had significantly lower contraction and Ca(2+)](i) transient amplitudes and SR Ca(2+) contents than control myocytes. At 0.6 mM Ca(2+)](o), contraction and Ca(2+)](i) transient amplitudes and SR Ca(2+) contents were significantly higher in ASNCX1 myocytes. At 1.8 mM Ca(2+)](o), contraction and Ca(2+)](i) transient amplitudes were not different between control and ASNCX1 myocytes. This pattern of contractile and Ca(2+)](i) transient abnormalities in ASNCX1 myocytes mimics that observed in rat MI myocytes. We conclude that downregulation of NCX1 in adult rat myocytes resulted in decreases in both Ca(2+) influx and efflux during a twitch. We suggest that depressed NCX1 activity may partly account for the contractile abnormalities after MI. |
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