The regulation of K+ transport across the red blood cell (RBC) membrane by haemoglobin (Hb) conformation was studied in carp, and the K+ transport mechanisms were identified. When a large proportion of Hb in the R quaternary structure was secured by oxygenation of blood at pH8.14, a net RBC K+ efflux was induced, which was accompanied by RBC shrinkage. This K+ efflux was resistant to ouabain and inhibited by furosemide and DIDS and by substitution of NO3 for Cl, showing it to result from a K+/Cl cotransport mechanism. Deoxygenation of the RBCs (Hb in T structure) eliminated the Cl-dependent K+ efflux and resulted in a net K+ uptake via the Na+/K+ pump. These changes were fully reversible. Nitrite-induced methaemoglobin formation in deoxygenated blood, which converts a large fraction of the T structure Hb into an R-like conformation, shifted the K+ uptake to a Cl-dependent K+ efflux similar to that seen in oxygenated cells. When the allosteric equilibrium between the R and T structures of Hb was gradually shifted towards the T state by decreases in pH, the Cl-dependent K+ efflux from oxygenated cells decreased. At pH7.52, where the Root effect caused a potent stabilisation of the T state, the K+ efflux was reversed to a net K+ uptake. A similar change was induced in methaemoglobin-containing deoxygenated blood, since low pH also favours a T-like conformation of metHb. The variable K+ fluxes could not be related to changes in membrane potential or pH but were always directly related to the experimental modulation of the relative proportions of R- and T-structure Hb. It is proposed that Hb conformation governs K+ movements via a different binding of T and R structures to integral membrane proteins, and that a large fraction of R-structure Hb triggers the Cldependent K+ efflux mechanism. Application of inhibitors and a substrate of prostaglandin and leukotriene synthesis did not influence the K+ efflux from oxygenated erythrocytes. However, a fraction of the K+ efflux from nitrite-treated deoxygenated cells was inhibited by nordihydroguaiaretic acid, suggesting that a slightly larger K+ efflux from these RBCs than from oxygenated RBCs was related to leukotriene production caused by nitrite entry. A much larger influx of nitrite to deoxygenated than to oxygenated RBCs was positively correlated with the distribution ratio of H+ and the membrane potential, supporting the view that nitrite primarily enters the cells via conductive transport. The physiological implications of the results are discussed.

This content is only available via PDF.