Rescue of contractile abnormalities by Na+/Ca2+ exchanger overexpression in postinfarction rat myocytes.
Previous studies on myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated increased cell length, reduced Na(+)/Ca(2+) exchange (NCX1) activity, altered contractility, and intracellular Ca(2+) concentration ([Ca(2+)](i)) transients. In the present study, we investigated whether NCX1 overexpression in MI myocytes would restore contraction and [Ca(2+)](i) transients to normal. When myocytes were placed in culture under continued electrical-field stimulation conditions, differences in contraction amplitudes and cell lengths between sham and MI myocytes were preserved for at least 48 h. Infection of both sham and MI myocytes by adenovirus expressing green fluorescent protein resulted in >95% infection, as evidenced by green fluorescent protein fluorescence, but contraction amplitudes at 6-, 24-, and 48-h postinfection were not affected. NCX1 overexpression in MI myocytes resulted in lower diastolic [Ca(2+)](i) levels at all extracellular Ca(2+) concentrations ([Ca(2+)](o)) examined, suggesting enhanced forward NCX1 activity. At 5 mM [Ca(2+)](o), subnormal contraction and [Ca(2+)](i) transient amplitudes in MI myocytes (compared with sham myocytes) were restored toward normal levels by overexpressing NCX1. At 0.6 mM [Ca(2+)](o), supranormal contraction and [Ca(2+)](i) transient amplitudes in MI myocytes (compared with sham myocytes) were lowered by NCX1 overexpression. We conclude that overexpression of NCX1 in MI myocytes was effective in improving contractile dysfunction, most likely because of enhancement of both Ca(2+) efflux and influx during a cardiac cycle. We suggest that decreased NCX1 activity may play an important role in contractile abnormalities in postinfarction myocytes.
Zhang
Xue-Qian
XQ
Weis Center for Research, Geisinger Medical Center, Danville, Pennsylvania 17822, USA.
Song
Jianliang
J
Qureshi
Anwer
A
Rothblum
Lawrence I
LI
Carl
Lois L
LL
Tian
Qiang
Q
Cheung
Joseph Y
JY
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism*
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D049452:Green Fluorescent Proteins; D002118:Calcium