Ouabain treatment of cardiac cells induces enhanced Na+-Ca2+ exchange activity

Inhibition of the cardiac Na+-K+-ATPase with cardiac glycosides causes a rise in internal Na+ and a subsequent increase in cellular Ca2+ due to the sarcolemmal Na+-Ca2+ exchange mechanism. We investigated the adaptation of cultured cardiac cells to prolonged elevation of internal Ca2+ after exposure to ouabain. Cultured neonatal rat heart cells were treated with 100 microM ouabain for 4-48 h. This ouabain concentration inhibited Na+-K+-ATPase activity by approximately 45% and caused modest cellular Ca2+ loading. We found that cells adapted to ouabain treatment by increasing the amount of sarcolemmal Na+-Ca2+ exchange activity by 50-90% over a 24-h period. Kinetic and immunological data indicate that the increase was due to increased numbers of functional exchangers. Neither total cellular nor total sarcolemmal protein content was affected by the ouabain treatment. These results may be relevant toward understanding the effects of therapeutic use of cardiac glycosides.