The ionic permeability of nerve membranes 



and Sepia axons, it has been found that during activity there is a net gain of sodium 

 and a roughly equal net loss of potassium which is more than large enough to account 

 for the changes in membrane potential. 



(4) The laws governing the movements of sodium and potassium during activity 

 have been studied in squid axons by Hodgkin, Huxley and Katz (1952), using a 

 technique by which the flow of current through a fixed area of nerve membrane 

 was measured while the membrane potential was varied in a strictly controlled 

 manner by a feed-back amplifier system. Comparison of results in normal and in 

 sodium-free sea water (choline being substituted for sodium) enabled the separate 

 contributions of Na+ and K+ ions to the total ionic current to be evaluated, and pro- 

 vided strong evidence that the sodium permeability of the membrane rises to a maxi- 

 mum soon after the initiation of an impulse and is subsequently inactivated, while 

 the potassium permeability only builds up after an appreciable delay. From a de- 

 tailed analysis of their results, Hodgkin and Huxley (1952) were able to show that 

 such a sequence of permeability changes could account quantitatively as well as 

 qualitatively for various well-known features of conduction and excitation. 



(5) The effects of varying the external sodium and potassium concentrations have 

 shown that in myelinated vertebrate nerve the active changes in membrane poten- 

 tial probably involve mechanisms similar to those in non-myelinated nerve. But the 

 excitable membrane is confined to a restricted area at each node of Ranvier, the 

 insulated internodal stretches of the fibre behaving as purely passive conductors. 



All the ionic movements I have described so far could occur without the inter- 

 vention of metabolism, since in each case they involve the transfer of ions from a 

 strong to a weaker solution. There is, however, ample evidence that metabolism does 

 play an essential part in the continued functioning of peripheral nerves. It has often 

 been shown, for example, that nerves deprived of oxygen will sooner or later cease to 

 conduct impulses, and that they will recover on the readmission of oxygen (see 

 Shanes, 1951). In a similar way, transmission through a mammalian sympathetic 

 ganglion is dependent on an adequate supply both of oxygen and of glucose (Larra- 

 bee and Bronk, 1951). It is also well known from the work of A. V. Hill and his 

 collaborators (see the review by Feng, 1936) that there is a rise in heat production 

 during nervous activity, and there has recently been a renewed interest in the increase 

 in oxygen consumption of stimulated nerves (Brink, Bronk, Carlson and Connelly, 

 1952), and in their carbon dioxide production, which varies according to the sub- 

 strate metabolized (Mullins, 1953). We must next consider the rather meagre evi- 

 dence as to the precise relation between nerve function and nerve metabolism. 



Shanes (1951) has described an experiment on a partially cleaned squid axon 

 which was mounted in a moist chamber and exposed to pure nitrogen. After about 

 thirty minutes of asphyxia, conduction failed, but the block probably arose from an 

 accumulation of potassium in the thin layer of external fluid, since it could be 

 relieved at once (though not for more than a few minutes) by flushing the apparatus 

 with nitrogenated sea water; a return to an atmosphere of oxygen also restored con- 

 duction, but only with a lag of some minutes. Hodgkin and I (1954^) have done a 

 similar experiment on a Sepia axon mounted in oil, in which we found that a normal 

 axon was able to maintain a steady state during stimulation at a low rate by re- 

 absorbing potassium as fast as it leaked out, while poisoning it with dinitrophenol 



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