Acute Trypanosoma cruzi infection is commonly associated with disorders of impulse conduction and muscle contraction in heart. In order to determine the extent to which receptor function changed in response to infection, infected neonatal rat cardiac myocytes in culture were compared with matched controls with regard to chronotropic response and Ca2+ 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 10-5M isoproterenol (ISO) and 10-6M norepinephrine (NE) with increases in beat rate of 34 and 40%, respectively. Effects of ISO on infected cells were similar, and adenylate cyclase activity was similar in control and infected cells when measured in the presence of ISO alone or in combination with Gpp(NH)p. NE produced a more marked chronotropic response in infected cultures and altered Ca2+ mobilization. NE treatment increased Ca2+ levels in control cardiac 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 infected 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 α-adrenergic-stimulated Ca2+ 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 Ca2+-mobilization responses to the α-adrenergic agonist NE are altered in T. cruzi-infected cardiac myocytes; the chronotropic response of similarly infected cells to the β-adrenergic agonist ISO was not affected. These data indicating that T. cruzi infection may be associated with a dissociation in responses to these agonists suggest a possible mechanism to explain, in part, the cardiac dysfunction characteristic of Chagas’ disease.
ASJC Scopus subject areas
- Infectious Diseases