In previous studies from out laboratory we have detailed the effect of Trypanosoma cruzi infection on the generation of intracellular second messengers such as cAMP and calcium. The mechanism of these effects seems to be at the level of the guanine nucleotide binding proteins. We have also described the effect of verapamil on the course of murine Chagas' disease, again implicating calcium as an important factor in the pathogenesis of the cardiomyopathy that attends this infection. We and others have made the observation that the extent of parasitism is unrelated to the functional impairment. Consequently, this has led us to an examination of the intracellular communication between infected and uninfected cells. In an effort to understand this relationship we will study coordinated communication between infected and uninfected myoblasts and between infected and uninfected cardiocytes via gap junctions. We will study whether T.cruzi infection results in altered expression of gap junctions. Toward this end we will compare gap junctions mRNA levels and immunolocalized gap junctions in infected and uninfected myoblasts and cardiocytes. We will also study the influence of infection on receptor-dependent and independent mobilization of intracellular calcium in single cells. The role of phospholipdid metabolism in this process will also be investigated. Finally, since we have already shown in a murine model that verapamil, a calcium channel blocker ameliorates the consequences of this infection on the heart we will determine the mode of action of this agent and other related compounds on intracellular calcium metabolism in infected myoblasts and cardiocytes. Alterations in intracellular calcium metabolism and gap junction expression may explain, in part, the contractility and electrical conduction abnormalities that attends Chagas' disease.