Gap Junctions and Chagas Disease

Abstract

Gap junction channels provide intercellular communication between cells. In the heart, these channels coordinate impulse propagation along the conduction system and through the contractile musculature, thereby providing synchronous and optimal cardiac output. As in other arrhythmogenic cardiac diseases, chagasic cardiomyopathy is associated with decreased expression of the gap junction protein connexin43 (Cx43) and its gene. Our studies of cardiac myocytes infected with Trypanosoma cruzi have revealed that synchronous contraction is greatly impaired and gap junction immunoreactivity is lost in infected cells. Such changes are not seen for molecules forming tight junctions, another component of the intercalated disc in cardiac myocytes. Transcriptomic studies of hearts from mouse models of Chagas disease and from acutely infected cardiac myocytes in vitro indicate profound remodelling of gene expression patterns involving heart rhythm determinant genes, suggesting underlying mechanisms of the functional pathology. One curious feature of the altered expression of Cx43 and its gene expression is that it is limited in both extent and location, suggesting that the more global deterioration in cardiac function may result in part from spread of damage signals from more seriously compromised cells to healthier ones.

The TGF-β Pathway as an Emerging Target for Chagas Disease Therapy

“…31 The reduction of gap junctions in T. cruzi-infected cells and T. cruzi-infected mice has been known since 1992 and has been extensively studied. 55,56 Gap junctions are plaques of intercellular channels composed of 12 connexin (Cx) molecules assembled into connexons. They connect the cytoplasm of adjacent cells, allowing propagation of electrical impulses.…”

Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease

“…We have found that infection with Trypanosoma cruzi , the causative agent of Chagas disease, alters gap junction expression in cultured cells obtained from heart and brain [12–14]. In T. cruzi -infected adipose tissue and cultured adipocytes there is upregulation of inflammatory mediators [15–18].…”

Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

“…It has been suggested that dampening of electrogenesis and bradyarrhythmias is due to the presence of autoantibodies against the second extracellular loop of cardiac M2 acetylcholine receptor and b2 adrenoceptor (26,27). Interestingly, some investigators have reported a decrease in the expression of connexin 43, a gap junction protein, in the infected cardiac myocytes (28). This implies a causal relationship between parasitic infection and cardiac conduction disorders.…”