80 D. NACHMANSOHN VOL. 4 (iQSO) 



which make this accelerated ionic flow possible, and others which restore the resting 

 condition. Experimental evidence that such events actually take place during the passage 

 of the impulse has been obtained by observations of Cole and Curtis^^ carried out 

 with the giant axon of Squid. These investigators measured the impedance changes 

 with alternating current of varying frequency applied across the nerve fibre. The 

 impedance was always reduced during the passage of the impulse. Analysing their 

 results, they concluded that the membrane resistance breaks down during activity from 

 about 1000 ohms per square centimeter to about 40 ohms per square centimeter. 



The assumption of a process in the membrane responsible for the electrical mani- 

 festations is not in contrast but in full agreement with all classical views. As was stated 

 by Keith Lucas and Adrian^* more than 30 years ago, all facts indicate that the 

 energy for the propagation of the nerve impulse cannot be derived from the stimulus 

 itself as in the case of a sound wave. According to the English investigators the energy 

 must be supplied locally by a "propagated disturbance". The most likely assumption 

 as to the nature of the "propagated disturbance" is that of a series of chemical reactions 

 producing a change of the proteins or lipoproteins of the membrane and resulting in an 

 increased permeability. Some kind of trigger mechanism must be responsible for the 

 change by which the ionic concentration gradient, inactive in rest, becomes effective. 

 This concentration gradient appears to be the most probable source of the electromotive 

 force. The change in the membrane required for this process must be, from the thermo- 

 dynamic point of view, associated with an irreversible loss of energy. The reversal will 

 require energy supply which can be conceivably derived from chemical reactions only. 

 It is remarkable that Keith Lucas {I.e.) in logical conclusion of his views postulated 

 that conduction must be associated with heat production, although at that time all 

 attempts to demonstrate it had failed. In 1926, however, A. V. Hill and his associates 

 were able to demonstrate heat production associated with nerve activity after they had 

 developed the recording instruments to an amazingly h'gh degree of perfections^. In the 

 same year evidence was obtained by Gerard and Meyerhof that conduction is accom- 

 panied by extra oxygen uptake^^. 



These investigations have established the experimental basis for the assumption 

 that conduction is associated with chemical reactions. The finer mechanism, however, 

 remained unknown. A. V. Hill's Liversidge lecture: Chemical Wave Transmission in 

 Nerve, delivered in 1932, was a challenge to biochemists to approach this central problem 

 of neurophysiologyS^^. Without a satisfactory answer as to the nature of the chemical 

 changes generating the flow of current, no decisive progress in the understanding of the 

 mechanism of nerve function will be achieved. The difficulty of finding this answer is 

 easily understood if we consider the information obtained by the physical recordings. 

 The initial heat per gram nerve per impulse in a frog sciatic nerve is of the order of 

 magnitude of io~^ gcal. The chemical reactions involved in the primary event must take 

 place within one-tenth of a millisecond or less. Reactants in a process of such a high speed, 

 metabolized in amounts of such a small order of magnitude, cannot be measured directly. 



Otto Meyerhof's pioneer work on muscular contraction has shown how much 

 information as to the mechanism of cellulan function may be obtained by the study of 

 enzymic reactions and by correlating them with events recorded with physical methods on 

 the living cell. By the successful linking of cellular metabolism and function Meyerhof's 

 work opened new pathways and was perhaps still more revolutionary than in other fields. 



It was under the inspiration obtained in Professor Meyerhof's laboratory that 

 References p. 93I95. 



