TRYPANOSOMA-CRUZI - EFFECTS OF INFECTION ON RECEPTOR-MEDIATED CHRONOTROPY AND CA2+ MOBILIZATION IN RAT CARDIAC MYOCYTES

Acute Trypanosoma cruzi infection is commonly associated with disorder s of impulse conduction and muscle contraction in heart. In order to d etermine the extent to which receptor function changed in response to infection, infected neonatal rat cardiac myocytes in culture were comp ared with matched controls with regard to chronotropic response and Ca 2+ mobilization following the application of adrenergic agonists. At 7 -9 days in culture (5-7 days postinfection), spontaneous beat rates of control myocytes were four times as rapid as those in infected cells. Control cells responded to 10(-5) M isoproterenol (ISO) and 10(-6) M norepinephrine (NE) with increases in beat rate of 34 and 40%, respect ively. Effects of ISO on infected cells were similar, and adenylate cy clase activity was similar in control and infected cells when measured in the presence of ISO alone or in combination with Gpp(NH)p. NE prod uced a more marked chronotropic response in infected cultures and alte red Ca2+ mobilization. NE treatment increased Ca2+ levels in control c ardiac myocytes from 51.8 +/- 4.4 to 113 +/- 16 nM (in 0 Ca2+ medium) and from 85.2 +/- 6.8 to 131.3 +/- 24.5 nM (1 mM external Ca2+). In in fected cardiac myocytes, NE increased Ca2+ from 116.8 +/- 17 to 164.7 +/- 9.6 nM (in 0 Ca2+ medium) and from 132.2 +/- 13.2 to 162.5 +/- 0.3 nM (1 mM Ca2+ medium). Thus, basal and alpha-adrenergic-stimulated Ca 2+ levels were higher in infected than uninfected myocytes regardless of the extracellular Ca2+ levels, although the fractional increase in infected myocytes was significantly lower than that in controls (1.4- and 1.2-fold vs 2.2- and 1.5-fold). Therefore, both chronotropic and C a2+-mobilization responses to the alpha-adrenergic agonist NE are alte red in T. cruzi-infected cardiac myocytes; the chronotropic response o f similarly infected cells to the beta-adrenergic agonist ISO was not affected. These data indicating that T. cruzi infection may be associa ted with a dissociation in responses to these agonists suggest a possi ble mechanism to explain, in part, the cardiac dysfunction characteris tic of Chagas' disease. (C) 1994 Academic Press, Inc.