Effects of impaired Ca2+homeostasis on contraction in postinfarction myocytes

Abstract

The significance of altered Ca2+ influx and efflux pathways on contractile abnormalities of myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) was investigated by varying extracellular Ca2+concentration ([Ca2+]o, 0.6–5.0 mM) and pacing frequency (0.1–5.0 Hz). Myocytes isolated from 3-wk MI hearts were significantly longer than those from sham-treated (Sham) hearts (125 ± 1 vs. 114 ± 1 μm, P < 0.0001). At high [Ca2+]oand low pacing frequency, conditions that preferentially favored Ca2+ influx over efflux, Sham myocytes shortened to a greater extent than 3-wk MI myocytes. Conversely, under conditions that favored Ca2+ efflux (low [Ca2+]oand high pacing frequency), MI myocytes shortened more than Sham myocytes. At intermediate [Ca2+]oand pacing frequencies, differences in steady-state contraction amplitudes between Sham and MI myocytes were no longer significant. Collectively, the interpretation of these data was that Ca2+ influx and efflux pathways were subnormal in MI myocytes and that they contributed to abnormal cellular contractile behavior. Because Na+/Ca2+exchange activity, but not whole cell Ca2+ current, was depressed in 3-wk MI rat myocytes, our results on steady-state contraction are consistent with, but not proof of, the hypothesis that depressed Na+/Ca2+exchange accounted for abnormal contractility in MI myocytes. The effects of depressed Na+/Ca2+exchange on MI myocyte mechanical activity were further evaluated in relaxation from caffeine-induced contractures. Because Ca2+ uptake by sarcoplasmic reticulum was inhibited by caffeine and with the assumption that intracellular Na+ and membrane potential were similar between Sham and MI myocytes, myocyte relaxation from caffeine-induced contracture can be taken as an estimate of Ca2+ extrusion by Na+/Ca2+exchange. In MI myocytes, in which Na+/Ca2+exchange activity was depressed, the half time of relaxation (1.54 ± 0.14 s) was significantly ( P < 0.02) prolonged compared with that measured in Sham myocytes (1.10 ± 0.10 s).