The control of Na+/H+ exchange by molecular oxygen in trout erythrocytes. A possible role of hemoglobin as a transducer.

It has previously been shown that addition of catecholamines to a suspension of trout erythrocytes induces an enlargement of the cells owing to an uptake of NaCl mediated by a cAMP-dependent, amiloride-sensitive Na+/H+ exchange. In this article, we show that the change in cell volume induced by catecholamines is much greater when the erythrocytes are incubated in N2 than when they are in O2. This difference is explained by an inhibition of the cAMP-dependent Na+/H+ exchange by O2. The inhibition is not reversed in cells incubated in O2 but poisoned with cyanide. It cannot be explained by a difference in the content of cAMP in O2 and in N2. In a CO atmosphere, in which the cells are anoxic, swelling and Na permeability are not increased as they are in N2: in CO, the cells behave as they do in O2. Moreover, cells previously exposed to CO and then put in an N2 atmosphere do not show the expected increase in Na+/H+ exchange. This strongly indicates that the binding of CO to hemoglobin, which persists during the subsequent exposure to N2, is the primary event responsible for the inhibition. As CO substitutes for O2 in binding to hemoglobin, the effect of O2 in the control of Na+/H+ exchange is probably explained by this interaction with heme. (Allen and McManus [1968. Biophysical Journal. 8:125a] previously described a similar effect of CO on passive Na permeability in duck red cells.) It is proposed that the hemoglobin, by interacting differently, according to its degree of oxygenation, with the cytoplasmic segment of band 3 protein, may influence some transport function, such as Na+/H+ exchange. The physiological significance of a control of Na+/H+ exchange by molecular O2 is discussed.