Effects of Na+/Ca2+ exchanger downregulation on contractility and [Ca2+]i transients in adult rat myocytes
| Autor: | Joseph Y. Cheung, Lois L. Carl, George M. Tadros, Qiang Tian, Jonathan Lytton, Lawrence I. Rothblum, Jianliang Song, Jeremy Dunn, Xue-Qian Zhang |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques Fura-2 Phosphodiesterase Inhibitors Physiology Genetic Vectors Green Fluorescent Proteins Muscle Fibers Skeletal Oligonucleotides Action Potentials Down-Regulation chemistry.chemical_element Calcium-Transporting ATPases Calcium Calsequestrin Sodium-Calcium Exchanger Adenoviridae Sarcoplasmic Reticulum Calcium-Transporting ATPases Rats Sprague-Dawley Contractility chemistry.chemical_compound Downregulation and upregulation Caffeine Physiology (medical) Internal medicine medicine Animals Myocyte Patch clamp Fluorescent Dyes Chemistry Myocardium Age Factors Myocardial Contraction Rats Luminescent Proteins Endocrinology Mutagenesis Indicators and Reagents Cardiology and Cardiovascular Medicine Intracellular |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 283:H1616-H1626 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00186.2002 |
| Popis: | Postmyocardial infarction (MI) rat myocytes demonstrated depressed Na+/Ca2+exchange (NCX1) activity, altered contractility, and intracellular Ca2+ concentration ([Ca2+]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) Ca2+-ATPase abundance, SR Ca2+uptake, resting membrane potential, action potential amplitude and duration, L-type Ca2+ current density and cell size were not affected by ASNCX1 treatment. At extracellular Ca2+ concentration ([Ca2+]o) of 5 mM, ASNCX1 myocytes had significantly lower contraction and [Ca2+]i transient amplitudes and SR Ca2+ contents than control myocytes. At 0.6 mM [Ca2+]o, contraction and [Ca2+]i transient amplitudes and SR Ca2+ contents were significantly higher in ASNCX1 myocytes. At 1.8 mM [Ca2+]o, contraction and [Ca2+]i transient amplitudes were not different between control and ASNCX1 myocytes. This pattern of contractile and [Ca2+]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 Ca2+ influx and efflux during a twitch. We suggest that depressed NCX1 activity may partly account for the contractile abnormalities after MI. |
| Databáze: | OpenAIRE |
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