Rescue of contractile abnormalities by Na /Ca exchanger overexpression in postinfarction rat myocytes

Zhang, Xue-Qian, Jianliang Song, Anwer Qureshi, Lawrence I. Rothblum, Lois L. Carl, Qiang Tian, and Joseph Y. Cheung. Rescue of contractile abnormalities by Na /Ca2 exchanger overexpression in postinfarction rat myocytes. J Appl Physiol 93: 1925–1931, 2002. First published August 16, 2002; 10.1152/japplphysiol.00583.2002.— Previous studies on myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated increased cell length, reduced Na /Ca2 exchange (NCX1) activity, altered contractility, and intracellular Ca2 concentration ([Ca2 ]i) transients. In the present study, we investigated whether NCX1 overexpression in MI myocytes would restore contraction and [Ca2 ]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 [Ca2 ]i levels at all extracellular Ca2 concentrations ([Ca2 ]o) examined, suggesting enhanced forward NCX1 activity. At 5 mM [Ca2 ]o, subnormal contraction and [Ca2 ]i transient amplitudes in MI myocytes (compared with sham myocytes) were restored toward normal levels by overexpressing NCX1. At 0.6 mM [Ca2 ]o, supranormal contraction and [Ca2 ]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 Ca2 efflux and influx during a cardiac cycle. We suggest that decreased NCX1 activity may play an important role in contractile abnormalities in postinfarction myocytes.