Molecular and functional studies of the gamma subunit of the sodium pump

This article reviews our studies of the gamma subunit of the sodium pump. Gamma is a member of the FXYD family of small, single transmembrane proteins and is expressed predominantly in the kidney tubule. There are two major variants of gamma which function similarly to bring about two distinct effects, one on K'(ATP) and the other, on K(K), the affinity of the pump for K+ acting as a competitor of cytoplasmic Na+. In this way, gamma is believed to provide a self-regulatory mechanism for maintaining the steady-state activity of the pump in the kidney. Our studies also suggest that K+ antagonism of cytoplasmic Na+ activation of the pump is relevant not only to the presence of gamma in the kidney, but probably some hitherto undefined factor(s) in other tissues, most notably heart. The interesting possibility that not only gamma but other members of the FXYD family regulate ion transport in a tissue-specific manner is discussed.