This paper describes experiments showing that one of the pathways of sodium transport across the red-cell membrane, sodium-lithium countertransport, is faster in patients with essential hypertension than in control subjects. This transport system accepts only sodium or lithium and is not inhibited by ouabain. The maximum rate of transport shows inherited differences. The mean maximum rate of sodium-lithium countertransport was found to be 0.55 +/- 0.02 (mean +/- S.E.M.) mmol (liter of red cells X hour)(-1) in a group of 36 patients with essential hypertension and 0.24 +/- 0.02 in 26 control subjects (P less than 0.001). The first-degree relatives of eight patients with essential hypertension and 10 control subjects had mean maximum rates of sodium-lithium countertransport of 0.54 +/- 0.05 and 0.23 +/- 0.02, respectively. Five patients with secondary hypertension had normal mean maximum rates of sodium-lithium countertransport. The relation between heritability of red-cell sodium-lithium countertransport and essential hypertension should be investigated further.

A B S T R A C T A model cell which controls its cation composition and volume by the action of a K-Na exchange pump and leaks for both ions working in parallel is presented. Equations are formulated which describe the behavior of this model in terms of three membrane parameters. From these equations and the steady state concentrations of Na, K, and C1, values for these parameters in high potassium (HK) and low potassium (LK) sheep red cells are calculated. Kinetic experiments designed to measure the membrane parameters directly in the two types of sheep red cells are also reported. The values of the parameters obtained in these experiments agreed well with those calculated from the steady state concentrations of ions and the theoretical equations. It is concluded that both H K and L K sheep red cells control their cation composition and volume in a manner consistent with the model cell. Both have a cation pump which exchanges one sodium ion from inside the cell with one potassium ion from outside the cell but the pump is working approximately four times faster in the H K cell. The characteristics of the cation leak in the two cell types are also very different since the H K cells are relatively more leaky to sodium as compared with potassium than is the case in the L K cells. Both cell types show appreciable sodium exchange diffusion but this process is more rapid in the L K than in the H K cells. I N T R O D U C T I O NO n e of the r e m a r k a b l e properties of living cells is their capacity to m a i n t a i n a relatively constant v o l u m e t h r o u g h o u t life. Since cells generally contain a large n u m b e r of charged macromolecules which c a n n o t pass t h r o u g h the plasma m e m b r a n e , osmotic forces p r o d u c e a constant t e n d e n c y to swell. In general, such systems can avoid swelling only if the hydrostatic pressure is sufficiently higher inside t h a n outside the cell, or if the cell surface is imThis work has been presented in part before

Melittin, a toxin of bee venom, is a cationic polypeptide composed of 26 amino acids. The six residues of the C-terminal end are polar and 19 of the 20 residues of the N-terminal end are hydrophobic. Exposure of the lecithin bilayer to melittin results in the formation of channels that are more permeable to anions that to cations. Unilateral addition of melittin produces a voltage-dependent increase in membrane conductance when the side where the polypeptide is present in made positive but not when it is made negative. At a fixed voltage, the conductance increases with the fourth power of the melittin concentration in the aqueous phase. At a fixed peptide concentration, the conductance increases approximately e-fold per 6-mV increase in the electrical potential difference across the membrane. These results suggest that four melittin monomers are needed to form a channel and, furthermore, that a minimum of four equivalent electronic charges need to be displaced by the electrical field to explain the voltage dependence of the conductance.

Chemical reactions in the aqueous unstirred layers of solution adjacent to a membrane can have dramatic effects on the diffusion of solutes across that membrane. This is demonstrated by the diffusion of labeled salicylate and salicylic acid across a phospholipid bilayer membrane. Two types of chemical reactions are considered. The first is an isotopic exchange reaction between the ionic and nonionic forms of a weak acid, HA + *A(-) [unknown] H*A + A(-). This reaction provides a way of estimating the true membrane permeability to a highly permeant weak acid and also a way of estimating the thickness of the unstirred layers. The second chemical reaction, the dissociation of a weak acid, HA [unknown] H(+) + A(-), can be used to show how the presence or absence of buffers in the unstirred layers controls the net transport of permeant weak acids across a membrane. In principle, the addition of appropriate "antacid" buffers to salicylates can increase their rate of absorption from the stomach.