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Effects of monovalent cations on cardiac Na+, K+-ATPase activity and on contractile force
Abstract:
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.
Insights
Monovalent cations like rubidium (Rb+) and thallium (Tl+) inhibit the sodium-potassium pump (Na+, K+-ATPase), leading to a positive inotropic effect in heart muscle. This effect is independent of heart rate and distinct from cardiac glycosides.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Pharmacology
Background:
- The sodium-potassium pump (Na+, K+-ATPase) is crucial for maintaining cellular ion balance.
- Monovalent cations can influence Na+, K+-ATPase activity and cardiac contractility.
- Understanding these interactions is key to developing cardiac therapies.
Purpose of the Study:
- To investigate the relationship between Na+, K+-ATPase inhibition by monovalent cations and their resulting inotropic effects in guinea pig hearts.
- To compare the effects of various monovalent cations on cardiac enzyme activity and contractile force.
Main Methods:
- Assayed partially purified cardiac Na+, K+-ATPase activity in the presence of different monovalent cations (Rb+, Tl+, K+, Cs+, NH4+, Na+, Li+).
- Measured isometric contractile force in isolated guinea pig left atrial strips bathed in modified Krebs-Henseleit solution.
- Evaluated the influence of propranolol on cation-induced inotropic responses.
Main Results:
- Rubidium (Rb+) and thallium (Tl+) inhibited Na+, K+-ATPase activity, particularly at lower sodium concentrations.
- Rb+ and Tl+ induced dose-dependent positive inotropic effects, insensitive to propranolol, unlike transient effects of K+ and NH4+.
- The onset of Rb+ and Tl+-induced inotropy was independent of contraction frequency, distinguishing them from cardiac glycosides.
Conclusions:
- Monovalent cations that inhibit the Na+, K+-ATPase, specifically Rb+ and Tl+, produce a sustained positive inotropic response in cardiac tissue.
- This mechanism of action differs from that of cardiac glycosides and beta-adrenergic stimulation.
- Findings suggest potential therapeutic applications for Na+, K+-ATPase inhibitors in managing cardiac function.