title: Effects of Na(+)/Ca(2+) exchanger downregulation on contractility and [Ca(2+)](i) transients in adult rat myocytes.
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.
authors.affiliation: Department of Medicine, Geisinger Medical Center, Danville, Pennsylvania 17822, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Tadros
authors.forename: Xue-Qian
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Jianliang
authors.initials: J
authors.lastname: Song
authors.forename: Lois L
authors.initials: LL
authors.lastname: Carl
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Rothblum
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tian
authors.forename: Jeremy
authors.initials: J
authors.lastname: Dunn
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lytton
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Cheung
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000256:Adenoviridae / Q000235:genetics; D000367:Age Factors; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005456:Fluorescent Dyes; D016257:Fura-2; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D016296:Mutagenesis / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009841:Oligonucleotides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002155:Calsequestrin; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D009841:Oligonucleotides; D010726:Phosphodiesterase Inhibitors; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D049452:Green Fluorescent Proteins; D002110:Caffeine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2