Na+,K+-ATPase, the star of epithelial net transports: what do we know about tis own polarized distribution

Abstract

The cells of metazoan organisms exchange nutrients and wastes with an extremely thin layer of interstitial milieu, that would be quickly spoiled, were it not for a circulatory apparatus that constantly restores nutrients and takes away waste products by carrying them to and from large areas of epithelia (intestinal, renal, lung, gills, etc.), where they are finally exchanged with the external environment. Therefore metazoans ultimately depend on the ability of their epithelia to transport substances in a net amount towards the outside of the organism or in the opposite direction. In the second half of the Nineteen Century Emile Du Bois Raymond found that the frog skin maintains a spontaneous electrical potential across, and in 1904 G. Galeotti proposed that it was due to a higher Na+ permeability in the inward than in the outward direction, but his suggestion was rejected lest that it would be in violation of the first and second laws of thermodynamics (for reviews see Cereijido and Rotunno 1971, Cereijido et al. 2004). To circumvent this difficulty it was proposed that energy would be afforded by cellular metabolism. Yet this was also refuted because, according to Curie’s Principle, phenomena of different tensorial order cannot be coupled, i.e. since the transport of Na+ is a vectorial phenomenon (it occurs in the outside −> inside direction) it cannot be driven by a scalar phenomenon (in those days chemical reactions were assumed to be scalar, and therefore was not expected to proceed in a given direction of space). Half a century later electric and tracer methods unambiguously demonstrated that the frog skin can actually transport a net amount of Na+ in the inward direction, in the absence of an external electrochemical potential gradient. This demanded, of course, a closer look at the arguments that had stood in the way of accepting that metabolism can drive Na+ transport.