The Journal of General Physiology, Vol 99, 199-216, Copyright © 1992 by The Rockefeller University Press
Hemisodium, a novel selective Na ionophore. Effect on normal human erythrocytes
DM Kaji
Renal Section, Veterans Affairs Medical Center, Bronx, New York 10468.
Hemisodium is a novel Na ionophore that belongs to the class of compounds
called cryptands. These compounds possess an electron-rich cavity for
binding of cations and are conformationally organized during synthesis to
favor the selective binding of one cation over another. In media containing
145 mM NaCl and 5 mM KCl, hemisodium (10(-5) M) increased erythrocyte Na
content from 23 to 345 mmol/kg.dry cell solid (dcs) over 4 h and increased
water content from 1.8 to 3.5 liter/kg.dcs over the same period. K content
decreased somewhat over the same time period, but this fall in K content
was prevented entirely by incubation in either low Na media (to prevent net
Na entry) or in Cl free media. Thus, the decrease in K content in high NaCl
media was due to cell swelling, which activated KCl cotransport, and not
due to a direct action of hemisodium on K permeability. Hemisodium-mediated
Na transport was conductive, because erythrocyte membrane potential (Vm),
determined by diS-C3-5 fluorescence, changed from -9 to +22 mV in high Na
media in the presence of hemisodium and DIDS. In cells equilibrated with
sulfamate, an anion with low conductive permeability, Vm changed 54 mV per
10-fold change in external Na concentration with the addition of
hemisodium. In contrast, a 10-fold change in the external concentration of
K, Rb, Cs, or T1 failed to alter Vm in the presence of hemisodium,
suggesting a high Na specificity of the ionophore. Na conductance
determined from net fluxes increased from 0.04 to 5.2 microS/cm2 with 10
microM hemisodium, and with that concentration the ratio of Na to K
conductance was 45:1. Among the Na ionophores available so far, hemisodium
appears to have the greatest specificity. Hemisodium may be a valuable tool
in membrane transport studies.
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