Sodium and Potassium Sensitivity of Calcium Uptake and Calcium Binding by Dog Cardiac Microsomes

Abstract

Concentrations of KCl and NaCl below 1.0 M increased Ca uptake (in the presence of oxalate) by dog cardiac microsomes purified on sucrose density gradients; higher concentrations of these salts decreased Ca uptake. At lower microsome concentrations, where calcium uptake was maximal, replacement of KCl by equimolar amounts of NaCl decreased both the rate and extent of Ca uptake. The uptake of Ca in mixtures of NaCl and KCl was that expected from the presence of each cation alone, and bore no obvious relationship to the (Na ⁺ + K ⁺ )-activated ATPase associated with sodium transport. Ca binding (in the absence of oxalate) was increased by concentrations of NaCl and KCl up to approximately 0.12 M when the reaction mixture contained 5 mM ATP; higher concentrations of the alkali-metal salts reduced Ca binding. A similar dual action of Na ⁺ and K ⁺ on Ca binding was seen in the absence of ATP, but Ca binding was maximal at approximately 0.01 M KCl. The reduced Ca binding at high concentrations of KCl in the presence of ATP showed some characteristics suggesting competition between K ⁺ and Ca ²⁺ for a single binding site, but double reciprocal plots of the data did not meet the strict criteria for a classical competitive reaction. Thus, while these microsomal membranes show some of the properties of an ion exchanger, these interactions are more complex, in that, at low ionic strengths, Ca binding is facilitated by addition of alkali-metal salts. Ca binding was not altered by replacing K ⁺ with Na ⁺ , and specific competition between Na ⁺ and Ca ²⁺ was not seen in deoxycholate-treated or sonicated microsomes. Thus, the site for the proposed Na ⁺ -Ca ²⁺ competition that controls myocardial contractility has not been found.