HANDBOOK OF PHYSIOLOGV 



NEUROPHYSIOLOGY I 



Stances that the observed membrane potential ex- 

 ceeds the value given by equation (12-1), one is 

 forced to believe that the resting potential is gener- 

 ated primarily by some electrochemical mechanism 

 other than the diffusion of the potassium ion. This 

 type of evidence against the potassium theory has 

 been expressed by several in\estis;ators though not 

 in a written form until the recent work of Shaw et al. 



(109)- 



The electrochemical nature of the plasma mem- 

 brane is not yet clearly understood. Osterhout (94), 

 Beutner (ii) and others assume that the resting 

 potential is maintained across an oil (nonaqueous) 

 layer. Teorell (139), SoUner (112) and others have 

 developed the concept of a charged porous mem- 

 brane as the site of bioelectric potential. .Shedlo\'skv 

 (iio) stressed the asymmetry of the membrane with 

 respect to two surfaces and the possible role of protons 

 in generation of the bioelectric potentials. 



To explain the divergence of the obser\ed resting 

 potential from the Nernst equation, Hodgkin (55) 

 used the modified Goldman equation (42). There is 

 .some doubt as to the applicability of this equation 

 to li\ing cells, because of the assumption of a uniform 

 field (i.e. no charge in the membrane) adopted in 

 deriving this equation (139, p. 338). Boyle & Conway 

 (17) found that the ratio of chloride across the muscle 

 fiber membrane is close to the ratio [K]o/[K], and 

 argued that the resting potential of the skeletal 

 muscle fiber is a Donnan potential. There are, how- 

 ever, some arguments against this notion (44). 



Actum Poleiilial 



There is at present only one widelv accepted 

 theory of action potential production. That is the 

 so-called sodium theory postulated by Hodgkin & 

 Huxley (57, 58, 59). Previously Nachmansohn 

 (89) advanced a theory in which acetylcholine is 

 assumed to play a decisive role in action potential 

 production. Recently, however, he shifted his effort 

 toward an attempt to supply a biochemical basis 

 for the sodium theory (90). 



This theory started with the de\elopmcnt of the 

 modern technique of recording and controlling the 

 intracellular potential. When it was found that the 

 amplitude of the membrane action potential is sub- 

 stantially larger than the resting potential across the 

 memjjrane (p. 84), physiologists realized that Bern- 

 stein's postulate as to the origin of the action potential 

 (p. 117) is incorrect. The finding of Hodgkin & 

 Katz (62^ that the amplitude of the action potential 



of the squid giant axon varies with approximately 

 58 mv times the logarithm of the concentration of 

 sodium in the external medium (p. 93) has led 

 the.se British physiologists to postulate that the mem- 

 brane potential at the peak of acti\its- is determined 

 by the concentration gradient of the .sodium ion 

 across the axon membrane. (According to this pos- 

 tulate, the amplitude of the action potential should 

 vary with 58 m\- times the logarithm of the intracel- 

 lular concentration of sodium; however, it is difficult 

 in practice to alter the sodium concentration in a 

 wide range.) 



Hodgkin & Huxley (59) elaborated this concept 

 further and explained the mechanism of action po- 

 tential production by assuming that the increase in 

 the membrane conductance during activity (p. 89) 

 is a specific increase of permeaijility to sodium ions. 

 They tried to substantiate this idea by voltage clamp 

 experiments (p. 91). Their success in reconstruct- 

 ing the action potential from the data obtained by 

 the voltage clamp technique is often regarded as 

 sufficient proof of the sodium theory. 



The diatjram in figure 36, right, shows the equiva- 

 lent circuit of the excitable membrane postulated in 

 the theory. When the membrane is at rest, the con- 

 ductance of the membrane is maintained by the per- 

 meabilit\' of the membrane to potassium ions; i.e. 

 gK » gsii! where gk is the 'potassium conductance' 

 and g^a the 'sodium conductance' of the membrane. 

 This situation should iiring the potential of the 

 resting membrane close to E^i which is defined by 

 equation (12-1). E^ia in the diagram represents the 

 'sodium equilibrium potential' defined ijy the equa- 

 tion of the type of equation (12-1) for the sodium 

 ion; the polarity of E^., is opposite to that of Ek- If 

 g^:, increases at the peak of activity to a \alue well 

 aboN'e gK, the niemljrane potential should approach 



FIG. 36. Right. ■ The equivalent circuit proposed by Hodgkin 

 & Hu.xley to represent tiie membrane of the squid giant 

 axon. Left: The state of an axon carrying an impulse proposed 

 by the same authors. The signs 4- and — indicate the electric 

 charges on the capacity which are assumed to determine the 

 membrane potential. Note that this concept of charges on the 

 condenser determining the membrane potential is inapplicable 

 to the circuit diagram of fig. 9C. 



