Red Cell Membrane Structure and Ion Transport

The red cell in man is a biconcave disk, some 8.4/z in diameter, 2.4 # thick at its widest portion, and 1/z thick at its narrowest. I t is bounded by a membrane primarily composed of protein and lipid, the latter sufficient in amount to cover the red cell with a layer two molecules thick. The lipid layer is bounded on the outside, and possibly on the inside, by a layer of protein. The thickness of the membrane is not known accurately since the most reliable studies, those made with the electron microscope and by optical refraction, are necessarily made with dried material. The best estimates of membrane thickness lead to values of the order of 100/~. Within the human red cell, there is a high K concentration, 143 mu/ l i te r cell water, and a low Na concentration, 13.9 rn~/liter cell water. In the environment, the situation is reversed, since plasma contains 5.0 mM K and 154 mM Na/li ter plasma water (1-3). The present paper is concerned with the role of the cellular membrane in the creation and maintenance of these sharp differences in ionic composition across a barrier that is only a few molecules thick, a problem common to a wide variety of living cells. The conclusions are based on studies carried out in this laboratory in company with a number of associates, including R. Villegas, D. H. P. Streeten, V. Sidel, C. V. Paganelli, D. Goldstein, G. L. Gold, T. J. Gill, J. Evans, and T. C. Barton. The passage of alkali cations across the red cell membrane is very Slow, 3.1 rnM Na and 2.1 m_M K/l i ter cell hour (1, 2). In the case of the principal intracellular cation, K, this corresponds to a half-time for exchange of 31 hours. In contrast, C1, the principal anion, enters the red cell freely and exchanges with a half-time of 0,24 seconds (4). Since the electrophoretic mobilities of these two ions are closely similar, this difference is commonly interpreted in terms of a positive charge barrier in the channels which connect the interior of the cell with its environment. The charge density required to produce this 5 X 10Lfold difference in rates of entrance may be calculated approximately according to the equations given by Meyer and Sievers (5). This calculation is independent of the dimensions of the channels through which the ions are presumed to pass, and leads to a charge density within the channels of 106 M/liter. Since water is present at a concentration somewhat less than 55 M/liter, the charge density of 106 M/liter is clearly impossible of achievement. However, as Sollner has pointed out (6), in the limit when the channels are Small enough, a single positive charge will suffice to block the