Comparative species studies on the effect of monovalent cations and ouabain on cardiac Na⁺,K⁺ adenosine triphosphatase and contractile force

The effects of ouabain, Rb⁺ and Tl⁺ on Na⁺,K⁺ adenosine triphosphatase (Na⁺,K⁺ ATPase; Mg⁺⁺ dependent, Na⁺,K⁺ activated ATP phosphohydrolase, EC 3.6.1.3) and contractile force were compared in guinea pig and rat hearts. Although ouabain produced a dose dependent positive inotropic effect in rat as well as in guinea pig atrial preparations, concentrations of ouabain needed to produce comparable positive inotropic effects were more than an order of magnitude higher in rats than in guinea pigs. Additionally, the time to reach the plateau of the inotropic response was significantly shorter in rat than in guinea pig atrial preparations. Concentrations of ouabain needed to produce comparable inhibition of cardiac Na⁺,K⁺ ATPase in vitro observed with partially purified cardiac enzyme preparations were also more than an order of magnitude higher in rats than in guinea pigs. In contrast, only minimal differences were observed either in the sensitivity of cardiac Na⁺,K⁺ ATPase to the inhibitory effects of Rb⁺ or Tl⁺ in rat and guinea pig enzyme preparations or in the sensitivity of rat and guinea pig atrial preparations to the positive inotropic action of Rb⁺ or Tl⁺. In both species, the onset of the positive inotropic response to Rb⁺ was rapid and that of the inotropic response to Tl⁺ was slow; hence there was no difference between rat and guinea pig atrial preparations with respect to the development of the positive inotropic response to these cations. Although Na⁺,K⁺ ATPase activity was assayed with ventricular tissues and the contractile force with atrial preparations, the sensitivity of atrial and ventricular tissues and the contractile force with atrial preparations, the sensitivity of atrial and ventricular Na⁺,K⁺ ATPase to ouabain appears to be the same. Thus, the response of cardiac Na⁺,K⁺ ATPase to various inhibitors appears to be related to the positive inotropic response of isolated atrial preparations with these agents. This finding supports the hypothesis that the inhibition of cardiac Na⁺,K⁺ ATPase is related to the enhancement of cardiac contractile force.