440 The Molecular Basis of Nerve Conduction /24 : 2 



are distributed in the opposite fashion. On the other hand, equilibrium 

 thermodynamics demands that the values of G be equal on the two sides 

 of the membrane for all ionic species present. In other words, the 

 ratio of the Na + concentration inside and outside muscle fibers is 

 in complete disagreement with the belief that Na + ions were free to 

 permeate the fiber membrane which acted as a passive semipermeable 

 membrane. 



However, tracer experiments show that Na + ions do pass through the 

 membrane in both directions. Thus, there can be little doubt that the 

 Na + concentrations are maintained at nonequilibrium ratios by active 

 transport out of the fiber at the expense of metabolic energy. 



If the membrane were suddenly to become much more permeable to 

 Na + , one would expect the membrane pump to be completely shunted 

 by the membrane permeability. If this occurred, the membrane 

 potential should reverse in sign, approaching that predicted by Equation 3 

 for Na + . Such an effect is observed at the peak of the spike potential. 

 Various types of studies attempting to unravel the molecular details of 

 how this occurs are discussed in the following sections. 



2. Quasi-Static Analogs 



The first type of study discussed in this section attempts to mimic the 

 action potential by direct currents which are too weak to elicit a trans- 

 mitted spike potential. This model has been pursued most fully by 

 Tobias and is discussed in Reference lb. Tobias points out that when 

 a spike potential travels down an axon, local currents will flow, having 

 the form shown in Figure 2. Similar electrical currents are produced 

 by a subthreshold direct current, as is shown in Figure 3. The figures 

 indicate that a subthreshold direct current does mimic the currents 

 accompanying the conduction of a spike potential. The current in the 

 anodal region is directed from the outside region into the axon just as 

 are the currents in the recovering part of the axon after the spike has 

 passed. Similarly, the currents near the cathode in Figure 3, and near 

 the part about to be excited, Figure 2, both flow from within the axon 

 into the external medium. 



In other words, the direct currents accompanying subthreshold 

 stimulation are similar in direction to those accompanying the spike 

 potential. Although the changes per unit time may be small, the sub- 

 threshold current can be maintained indefinitely. By observing the 

 results of prolonged subthreshold currents, it is hoped to emphasize 

 physical and chemical changes accompanying spike conduction. The 

 situation represented in Figure 3 is then the analog of the spike potential 



