382 ANNALS NEW YORK ACADEMY OF SCIENCES 



cutting the muscle, but often as a reversible process and obviously in- 

 dicative of the greatest permeating power. The other alkali cations 

 appeared to be less effective, in this order: potassium, rubidium, 

 sodium, lithium; potassium and rubidium producing negativity, as 

 compared to sodium, while lithium produces positivity. This was 

 interpreted as being due to swelling or shrinking of hydrophilic colloids, 

 which were assumed to be the chief constituents of the plasma mem- 

 brane. Later, the same series was met by Michaelis with non-colloidal, 

 rigid, dried collodion membranes. His findings seemed to fit in best 

 with the concept of an ionic sieve. For, taking into consideration the 

 shells of water dipoles around the ions, the effective ionic volume ap- 

 pears to be smallest with potassium, largest with lithium. But, as 

 will be seen later, the differences are better correlated with adsorption, 

 which, according to Gouy, Frumkin, and others, increases with decreas- 

 ing hydration of the ions, potassium being most, lithium least, adsorbed. 

 The membrane theory postulates that, as in the case of the suffi- 

 ciently dried collodion membrane, which is permeable only to potassium 

 ion, strength and direction of the injury potential are dependent upon 

 the ratio of potassium inside to potassium outside. In other words, 

 the surface of muscle or nerve behaves as a potassium-electrode, 

 potassium inside being constant and about 20 to 40 times greater than 

 potassium outside. Therefore, by raising potassium outside, the EMF 

 of an injured (cut) muscle should be decreased to zero, if potassium 

 outside is equal to potassium inside, and its direction should be re- 

 versed, if potassium outside is greater than potassium inside. My own 

 early experiments (1905) failed to show the reversal, because, in con- 

 trast to the rigid, dried collodion membrane, the ion selectivity of the 

 plasma membrane is lost, due to its colloidal behavior: in other words, 

 due to the swelling and disintegrating, even to the cytolyzing effect of 

 higher potassium, especially after some lapse of time. However, the 

 postulate of a reversal complies with recent observations of Hodgkin 

 and Huxley,' and of Curtis and Cole," in a particularly striking way. 

 These authors, leaning upon Osterhout's* studies on the "impaled" 

 giant plant cells ( Valonia) , pushed a microelectrode into the axoplasma 

 of the giant nerve fiber of the squid, along its axis, so that its tip was 

 placed just opposite to the outside electrode, and they thus measured 

 the membrane potential directly across the wall. The potential was 

 found, in the case of the squid nerve, to be, on an average, 50 mV. 

 Then, upon raising potassium outside to about 18 times normal, the 

 resting potential was decreased to zero, and upon raising it about 40 

 times normal, a reversal of 15 mV was observed. The corresponding 



