The Effects of Sickling on Ion Transport

Abstract

The conversion of red cells of patients with sickle cell anemia (S-S) from biconcave disk to sickle shape by removal of oxygen was found to increase the fraction of medium trapped in cells packed by centrifugation from 0.036 (S.E. 0.003) to 0.106 (S.E. 0.004). The fraction of water in the cells (corrected for trapped medium) was not affected by this shape transformation. Cation transport, however, was changed profoundly. S-S cells incubated in N2 rather than O2 showed net K loss with acceleration of both influx and outflux. That this change in K transport was due to the process of sickling was indicated by (1) the persistence of the effect in the absence of plasma, (2) the absence of the effect in hypoxic S-S cells in which sickling was inhibited by alkali or carbon monoxide, (3) the reversal of the effect when sickling was reversed by exposure to O2, and (4) the independence of the effect from such potentially important factors as age of the cell population. The acceleration of K transport by sickling is probably mediated by modification of the cell surface rather than the cell interior since concentrated sickle hemoglobin solutions in O2 or N2 did not show selective affinity for K. In molecular terms, the effect of sickling on K transport can be explained by presuming that the shape change (1) opens pathways for the free diffusion of K, and (2) accelerates K transport by a non-diffusion carrier process. The evidence for the former mechanism included (a) dependence of K influx into sickled cells on the concentration of K in the medium, and (b) increase in the total cation content of sickled cells with increasing pH. Observations suggestive of a carrier process included (a) the failure of sickled cell K concentration to become equal to external K concentration even after 48 hours, (b) the deviation of the flux ratio from that characteristic of diffusion, and (c) the dependence of K influx on glycolysis.

Volume-regulatory responses of Amphiuma red cells in anisotonic media. The effect of amiloride.

“…Although this equation assumes a steady state two-compartment system, flux values corrected for changes in cell K content using the non-steady state method of Tosteson et al (1955) yielded values that differed by at most 4% from those calculated with Eq. 4.…”

The sensitivity of Na⁺, K⁺ ATPase as an indicator of blood diseases

“…However, a low oxygen tension induces a rise in the intracellular pH, which is also a stimulus to glycolysis. In irreversibly sickled cells (ISC), even when oxygenated, the cell water and K + are low while Na + is moderately increased 21 . It is likely that the increases in ATPase activity suggested the presence of younger red blood cell population in sickling patients.…”

Molecular sieving action of the cell membrane during gradual osmotic hemolysis

“…The increase in Hbmembrane association appears to be correlated with an increase in cation permeability as demonstrated in Heinz-body-containing cells (Parker and Welt, 1972) and mimicked by thio reagents (Parker and Welt, 1972) and as reversibly demonstrated when Hb-S-containing cells are deoxygenated (Tosteson, 1955;Tosteson, Carlsen and Dunham, 1955). In support of the proposed increase in Hb-membrane association in deoxygenated cells, deoxygenation also increases cation permeability (Nathan and Shohet, 1970).…”