Effects of 2,4,6-triaminopyrimidine on the electromechanical properties of guinea-pig myocardium

Abstract

The effects of 2,4,6-triaminopyrimidine (TAP) were studied in vitro on transmembrane potential and contractility in guinea-pig myocardium. In electrically driven Langendorff-perfused hearts, the addition of 1 and 5 mM TAP produced an initial dose-dependent positive inotropic response with no change in resting tension. The activation process was studied by means of microelectrode and tension recording from isolated electrically driven guinea-pig left atrial preparations. TAP (1-10 mM) produced dose-dependent changes in both electrical and mechanical properties of the tissue. In particular, 1,5 and 10 mM TAP increased the action potential duration by approximately 20, 40 and 60% while also increasing contractile strength by approximately 30, 60 and 90%, respectively. The mechanical effects of TAP were also observed in the presence of 10 muM propranolol. Experiments on catecholamine-restored hearts which were depolarized by potassium indicated that the inotropic action of TAP was associated with slow calcium influx channels. The inotropic effects of TAP were reduced by D600, a calcium antagonistic agent. These data are consistent with a hypothesis that the inotropic actions of TAP result from a decrease in potassium conductance as a result of the inhibition of Ca++-K+ interactions at the inner surface of the myocardial membrane.