Sodium-Calcium Exchange in the Heart

A short historical perspective of the subject provides a basis for division of the chapter into two major components: (a) a discussion of the relation of sodium (Na) to calcium (Ca) in binding at the sarcolemmal and (b) a discussion of the relation as it pertains to transsarcolemmal transport. first indications that the Na ion might affect Ca movement in the heart appeared in 1921. The effect of lack of sodium shows a striking resemblance to the effect of strophanthidin (14). prophetic nature of this conclusion is discussed below. Von Wilbrandt & Koller (56) almost 30 years later developed the concept that the site of action of calcium in the heart is most probably the cell membrane, and proposed a CaolNa� rela­ tionship as being of importance in the control of the contractile response. In 1958 Liittgau & Niedergerke (32) proposed that Na and Ca ions com­ pete for anionic groups (R) at the cell surface (frog heart) on the basis of charge such that force was determined according to a CaolNa� relation­ ship. idea was that the Ca, once bound to an anionic component (R2-) according to 2Na + CaR � Na2R + Ca, would move across the membrane and activate contraction. control of force, via Ca, was placed at the cellular surface with little attention paid to possible events at the intracellular side of the sarcolemma. In 1964, Repke in a consideration of the mechanism of action of digitalis (48) and Langer in a consideration of the staircase response (24) raised the possibility that intracellular accumulation of Na might be linked to aug­ mented Ca influx, but no definitive mechanisms were offered. In 1968 Reuter & Seitz (51) found evidence for a membrane carrier system in the heart involving Na and Ca and demonstrated that Ca efflux rate was sensi-