The Physical State of K⁺ and Na⁺ in Living Cells

Abstract

The experimental studies of A. V. Hill and Kupalov (1930; Hill, 1930) on frog muscle led them to the conclusion that virtually all water and K⁺ exist in the free state in living cells. The persuasiveness of their arguments played a major role in the abandonment of the colloidal approach to cell physiology and led to the dominance of the membrane theory (Section 2.7). This trend was greatly enhanced by measurements of the high mobility and thermodynamic activity coefficient of K⁺ in living cells as well as by other evidence described in Section 5.1. In this chapter I present the results of the most recent studies on the subject, usually carried out with the aid of sophisticated techniques not available in the past. These results lead to conclusions that are dramatically different from what was once widely believed. Indeed, there now remains little doubt that virtually all the K⁺ in resting living cells exists in an adsorbed state. Before presenting the details of these new findings, and following up in depth on old ones, I want to remind the reader of the recent successful demonstration of ion binding on isolated proteins briefly mentioned in Section 6.2.5: When salt linkages are prevented from forming, all proteins studied adsorb K⁺, Na⁺, or other alkali metal ions in a selective manner and at a high enough level to match those seen in living cells (Section 11.2.2.2). Failure in the past to demonstrate the same played a major role in the acceptance of the pump theory (see Section 4.4.1).