HARRY GRUNDFEST I 25 



excitation phenomena (no) as well as the time course of increased membrane 

 conductance during the squid spike (9, 44, loi). 



Subsequent work (114) indicates that the independence of inward and 

 outward tlow of the same ion species, which was assumed in the derivation of 

 the theory, is not experimentally verified. Membrane impedance measurements 

 (9, 172) on the squid giant axon disclosed that the resistance of the membrane 

 rises very considerably above the resting level while the axon is still in the 

 hyperpolarized state, whereas the deduced K+ conductance (no) is presumed 

 to be still high. It has been suggested (9) that this increased resistance is due to 

 decreased K+ conductance produced by the hyperpolarization. Thus, while the 

 three processes postulated in the theory appear to exist in squid axon^ it is 

 likely that some modification of their kinetics would satisfy the new data. 



Each of the three processes of the Hodgkin and Huxley theory is a continuous 

 function of membrane potential and is described by an appropriate differential 

 equation. In the totality of their action, momentary excess of inward sodium 

 current over outward potassium current is the immediate trigger for the 

 onset of the spike. The subsequent decrease of sodium current by 'sodium 

 inactivation' below that of potassium current is the trigger for its subsidence. 

 The processes are analogous to those during the triggered pulse of a monostable 

 electronic circuit, in which the events can also be described by differential 

 equations. These processes therefore do not in themselves provide the trigger 

 for the spike, which must be sought in underlying molecular changes of the 

 membrane. The specific differences in rate and the independent course of 

 sodium and potassium conductance, as well as the process of sodium inactiva- 

 tion, indicate that the molecular mechanisms of sodium and potassium con- 

 ductance are probably different. The species of molecular change can only be a 

 matter of speculation at present and the model chosen depends upon individual 

 preference with respect to the various and conflicting theories of functional 

 membrane structure. In essence the assumed conductance processes represent 

 potential-dependent valving, selective for sodium and potassium, flow of the 

 ions being determined only by their electrochemical gradients. These flows 

 therefore should be independent of metabolic conditions, unlike the secretory 

 transport mechanism of the 'pumps' of the resting membrane. It is customary 

 to postulate that these ion-specific valves are achieved through specific mem- 



^ The frog nerve fiber does not appear to show increased K+ conductance during the spike 

 (176). The membrane resistance of the eel electroplaque appears to be higher during the 

 failing phase of the spike than at rest (2). The membrane resistance of cardiac fibers rises 

 about three-fold above the resting value during the plateau of the electrical response (185). It 

 is likely, therefore, that sodium conductance and inactivation and potassium conductance 

 have rather different kinetics in different tissues. For example, potassium conductance may 

 be very much delayed in the normal response of heart muscle. This could account for the 

 peculiar form of the response and impedance change. Chemical agents, by altering the 'valving' 

 kinetics, might thus alter the time course of the electrical phenomena. 



