Regional expression of sodium pump subunits isoforms and Na+-Ca++ exchanger in the human heart.

Cardiac glycosides exert a positive inotropic effect by inhib- iting sodium pump (Na,K-ATPase) activity, decreasing the driving force for Na 1 -Ca 11 exchange, and increasing cellu- lar content and release of Ca 11 during depolarization. Since the inotropic response will be a function of the level of ex- pression of sodium pumps, which are ab heterodimers, and of Na 1 -Ca 11 exchangers, this study aimed to determine the regional pattern of expression of these transporters in the heart. Immunoblot assays of homogenate from atria, ventri- cles, and septa of 14 nonfailing human hearts established expression of Na,K-ATPase a 1, a 2, a 3, b 1, and Na 1 -Ca 11 exchangers in all regions. Na,K-ATPase b 2 expression is negligible, indicating that the human cardiac glycoside re- ceptors are a 1 b 1,, a 2 b 1, and a 3 b 1. a 3, b 1, sodium pump activity, and Na 1 -Ca 11 exchanger levels were 30-50% lower in atria compared to ventricles and/or septum; differ- ences between ventricles and septum were insignificant. Functionally, the EC 50 of the sodium channel activator BDF 9148 to increase force of contraction was lower in atria than ventricle muscle strips (0.36 vs. 1.54 m M). These results de- fine the distribution of the cardiac glycoside receptor iso- forms in the human heart and they demonstrate that atria have fewer sodium pumps, fewer Na 1 -Ca 11 exchangers, and enhanced sensitivity to inotropic stimulation compared to ventricles. ( J. Clin. Invest. 1996. 98:1650-1658.) Key words: Na,K-ATPasecardiac contractilitydigitalis re- ceptorBDF 9148