Effects of monovalent cations on cardiac Na+, K+-ATPase activity and on contractile force.

The relationship between Na+, K+-ATPase inhibition by monovalent cations and their inotropic effect was studied in guinea pig hearts. The activity of partially purified cardiac enzyme was assayed in the presence of 5.8 mM KC1 and either 20 or 150 mM NaCl. Rb+ and Tl+ inhibited Na+, K+-ATPase activity, the magnitude of the inhibition by these cations being greater in the assay media containing lower Na+ concentrations. Tl+ produced a dose-dependent inhibition of Na+, K+-ATPase activity in the presence of 20 mM Na+ and 75 mM K+, a cationic condition similar to that of intracellular fluid. Other monovalent cations such as K+, Cs+, NH4+, Na or Li+ produced essentially no effect on the Na+, K+-ATPase activity or slightly stimulated it. In left atrial strips stimulated with field electrodes and bathed in Krebs-Henseleit solution (5.8 mM K+ and 145 mM Na+), addition of Cs+ failed to alter the isometric contractile force significantly. NH4+ and K+ caused a transient positive inotropic effect which was partially blocked by propranolol. The positive inotropic response to K+ was followed by a negative inotropic response. Rb+ produced a sustained, dose-dependent inotropic response reaching a plateau at 1-2 min, whereas Tl+ produced a dose=dependent positive inotropic effect which developed slowly over a 30-min period. The positive inotropic effects produced by Rb+ and Tl+ were insensitive to propranolol pretreatment. Concentrations of Tl+ and cardiac glycosides which produce similar inotropic effects appear to cause the same degree of Na+-pump inhibition. The onset of the positive inotropic response to Rb+ or Tl+ was not dependent on the number of contractions which is in contrast to the cardiac glycoside-induced inotropic response. Substitution of 20 mM LiCl for an equimolar amount of NaCl in Krebs-Henseleit solution produced a significantly greater inotropic response than that observed when sucrose was substituted for NaCl. It appears that, among monovalent cations, only sodium pump inhibitors produce a sustained positive inotropic response.