It has long been known that cardiac glycosides can inhibit the membrane sodium-potassium (Na+-K+) pump, raising intracellular Na+. However, at clinical concentrations of cardiac glycosides, a change in intracellular Na+that correlates with a change in cardiac contraction has been very difficult to demonstrate. The recent use of Na+-sensitive microelectrodes in the experimental laboratory has made intracellular Na+measurements possible. A doubling of contraction strength in vitro is associated with a change of only approximately 1 mMintracellular Na+. Another membrane transport system, the Na+-Ca2+exchange system, exchanges extracellular Na+ for intracellular Ca2+. If this system is responsible for regulating intracellular Ca2+, then it would be very sensitive to the transmembrane Na+ concentration gradient. This influence of intracellular Na+ on Na+-Ca2+exchange is thought to be the cellular basis of the positive inotropic action of digitalis. However, a number of issues remain unresolved, such as the extent of Na+-K+pump inhibition by the level of cardiac glycoside achieved clinically.
From the Cardiac Electrophysiology Laboratory, the Departments of Medicine and the Pharmacological and Physiological Sciences, The University of Chicago, Chicago, Illinois.