Alterations in G-protein-regulated transmembrane signalling induced in murine myocardium by coxsackievirus B3 infection.

OBJECTIVE

Cardiomyopathy is usually associated with marked alterations in myocardial transmembrane signalling. Although acute viral myocarditis may result in chronic cardiomyopathy in some cases, the possible consequences of viral infection on function of the myocardial signal-transducing complex have not been explored. Therefore, the present study was designed to investigate the G-protein-regulated adenylyl cyclase signalling system in murine myocardium during myocarditis induced by coxsackievirus B3 (CVB3) infection.

METHODS

We examined the functional characteristics of adenylyl cyclase as well as the function and distribution of beta-adrenoceptors, m-cholinoceptors and G-proteins in myocardial plasma membranes isolated from the hearts of mice with acute (7 days pi) or late phase (21 days pi) myocarditis and the obtained results were compared with the corresponding data determined in age-matched controls.

RESULTS

While the basal adenylyl cyclase activity was not significantly altered, the ability of forskolin, sodium fluoride and GTP gamma S to activate adenylyl cyclase was lowered by about 20% in samples from virus-infected animals. The level of Gs alpha in myocardial plasma membranes as well as the functional activity of Gs alpha was not affected by viral infection, but the Gi alpha content was increased by about 20%. The total number of beta-adrenoceptors in myocardial plasma membranes increased by about 12-15% due to higher content of the beta 2-adrenoceptor subtype. Although the agonist-binding parameters of beta-adrenoceptors were not significantly altered, the ability of these receptors to mediate stimulation of adenylate cyclase was markedly diminished (by 56-80%). The total number of m-cholinoceptors in samples derived from virus-infected mice increased considerably (by 29-59%) and a significant proportion of the receptors shifted to a higher affinity status, but their ability to transduce agonist signals was impaired.

CONCLUSIONS

These data are the first to demonstrate that several different sites of the myocardial G-protein-regulated adenylyl cyclase signalling complex are significantly altered in acute as well as in late phase of CVB3-induced myocarditis.