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Mechanisms involved in the stimulatory action of adenosine on cardiac ventricular automaticity

Objective



Adenosine, a metabolite whose production is increased during metabolic inhibition, is known to exert inhibitory effects on heart. Recently, however, it has been shown that low concentrations of adenosine (Ado) increase automaticity in the isolated right ventricle of the rat, whereas inhibition is seen at high concentrations. Both effects are antagonized by theophylline, suggesting interaction with an extracellularly located Ado receptor. The aim of the present project is to analyse at different levels the stimulatory effect of Ado:
1) characterization of the Ado receptor by radioligand studies; 2) pharmacological study of the interaction with adrenergic receptors; 3) analysis of the underlying electrophysiological changes in terms of ionic currents at the single cell level (patch electrode) and of the eventual concomitant changes in intracellular Ca concentration, using the indo-fluorescence method.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Katholieke Universiteit Leuven
Address
59,Naamsestraat
3000 Leuven
Belgium

Participants (2)

Fundação Calouste Gulbenkian
Portugal
Address
14,Rua Da Quinta Grande
2781 Oeiras
Universidad de Murcia
Spain
Address
Espinardo
30100 Murcia