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⁺]_o and 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⁺]_o and high pacing frequency), MI myocytes shortened more than Sham myocytes. At intermediate [Ca²⁺]_o and 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).

excitation-contraction; cardiac hypertrophy; heart; systolic dysfunction

This article has been cited by other articles:

				M. Maczewski and U. Mackiewicz Effect of metoprolol and ivabradine on left ventricular remodelling and Ca2+ handling in the post-infarction rat heart Cardiovasc Res, July 1, 2008; 79(1): 42 - 51. [Abstract] [Full Text] [PDF]

				G. R. Norton, D. G. A. Veliotes, O. Osadchii, A. J. Woodiwiss, and D. P. Thomas Susceptibility to systolic dysfunction in the myocardium from chronically infarcted spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H372 - H378. [Abstract] [Full Text] [PDF]

				X.-Q. Zhang, J. R. Moorman, B. A. Ahlers, L. L. Carl, D. E. Lake, J. Song, J. P. Mounsey, A. L. Tucker, Y.-m. Chan, L. I. Rothblum, et al. Phospholemman overexpression inhibits Na+-K+-ATPase in adult rat cardiac myocytes: relevance to decreased Na+ pump activity in postinfarction myocytes J Appl Physiol, January 1, 2006; 100(1): 212 - 220. [Abstract] [Full Text] [PDF]

				B. A. Ahlers, J. Song, J. Wang, X.-Q. Zhang, L. L. Carl, G. M. Tadros, L. I. Rothblum, and J. Y. Cheung Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes J Appl Physiol, June 1, 2005; 98(6): 2169 - 2176. [Abstract] [Full Text] [PDF]

				J. Song, X.-Q. Zhang, J. Wang, L. L. Carl, B. A. Ahlers, L. I. Rothblum, and J. Y. Cheung Sprint training improves contractility in postinfarction rat myocytes: role of Na+/Ca2+ exchange J Appl Physiol, August 1, 2004; 97(2): 484 - 490. [Abstract] [Full Text] [PDF]

				M. A. Mirza, X.-Q. Zhang, B. A. Ahlers, A. Qureshi, L. L. Carl, J. Song, A. L. Tucker, J. P. Mounsey, J. R. Moorman, L. I. Rothblum, et al. Effects of phospholemman downregulation on contractility and [Ca2+]i transients in adult rat cardiac myocytes Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1322 - H1330. [Abstract] [Full Text] [PDF]

				X.-Q. Zhang, A. Qureshi, J. Song, L. L. Carl, Q. Tian, R. C. Stahl, D. J. Carey, L. I. Rothblum, and J. Y. Cheung Phospholemman modulates Na+/Ca2+ exchange in adult rat cardiac myocytes Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H225 - H233. [Abstract] [Full Text] [PDF]

				X.-Q. Zhang, J. Song, A. Qureshi, L. I. Rothblum, L. L. Carl, Q. Tian, and J. Y. Cheung Rescue of contractile abnormalities by Na+/Ca2+ exchanger overexpression in postinfarction rat myocytes J Appl Physiol, December 1, 2002; 93(6): 1925 - 1931. [Abstract] [Full Text] [PDF]

				G. M. Tadros, X.-Q. Zhang, J. Song, L. L. Carl, L. I. Rothblum, Q. Tian, J. Dunn, J. Lytton, and J. Y. Cheung Effects of Na+/Ca2+ exchanger downregulation on contractility and [Ca2+]i transients in adult rat myocytes Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1616 - H1626. [Abstract] [Full Text] [PDF]

				I. Sjaastad, J. Bokenes, F. Swift, J. A. Wasserstrom, and O. M. Sejersted Normal contractions triggered by ICa,L in ventricular myocytes from rats with postinfarction CHF Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1225 - H1236. [Abstract] [Full Text] [PDF]

				J. Song, X.-Q. Zhang, L. L. Carl, A. Qureshi, L. I. Rothblum, and J. Y. Cheung Overexpression of phospholemman alters contractility and [Ca2+]i transients in adult rat myocytes Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H576 - H583. [Abstract] [Full Text] [PDF]

				U. Wisloff, J. P. Loennechen, S. Currie, G. L. Smith, and O. Ellingsen Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility, Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction Cardiovasc Res, April 1, 2002; 54(1): 162 - 174. [Abstract] [Full Text] [PDF]

				K. R Sipido, P. G.A Volders, M. A Vos, and F. Verdonck Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy? Cardiovasc Res, March 1, 2002; 53(4): 782 - 805. [Abstract] [Full Text] [PDF]

				X.-Q. Zhang, J. Song, L. I. Rothblum, M. Lun, X. Wang, F. Ding, J. Dunn, J. Lytton, P. J. McDermott, and J. Y. Cheung Overexpression of Na+/Ca2+ exchanger alters contractility and SR Ca2+ content in adult rat myocytes Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2079 - H2088. [Abstract] [Full Text] [PDF]

				L.-Q. Zhang, X.-Q. Zhang, T. I. Musch, R. L. Moore, and J. Y. Cheung Sprint training restores normal contractility in postinfarction rat myocytes J Appl Physiol, September 1, 2000; 89(3): 1099 - 1105. [Abstract] [Full Text] [PDF]

				L.-Q. Zhang, X.-Q. Zhang, Y.-C. Ng, L. I. Rothblum, T. I. Musch, R. L. Moore, and J. Y. Cheung Sprint training normalizes Ca2+ transients and SR function in postinfarction rat myocytes J Appl Physiol, July 1, 2000; 89(1): 38 - 46. [Abstract] [Full Text] [PDF]

				X.-Q. Zhang, Y.-C. Ng, R. L. Moore, T. I. Musch, and J. Y. Cheung In situ SR function in postinfarction myocytes J Appl Physiol, December 1, 1999; 87(6): 2143 - 2150. [Abstract] [Full Text] [PDF]