446 The Molecular Basis of Nerve Conduction /24 : 4 



blocked but the resting potential remains unaltered. If the ACh 

 hypothesis presented a complete picture of axon potentials, it would be 

 hard to understand why ACh would not accumulate slowly, completely 

 abolishing the resting potential. 



There are large gaps in the ACh hypothesis. Many compounds have 

 to be assumed whose existence cannot be demonstrated directly. Even 

 the bound, inactive form of ACh is not known. How or why ACh is 

 released by an oncoming action potential is unknown. How or at what 

 type of sites ACh increases permeability is not known. Nor does this 

 system throw any light on the Na + pump necessary to restore the resting 

 potential and the equilibrium ionic concentrations. 



To summarize this section briefly, the release of acetylcholine and its 

 hydrolysis by cholinesterase appear essential for the conduction of the 

 spike potential. In spite of this, neither is there a clear picture of the 

 role of these compounds on a molecular scale, nor do they help as yet in 

 understanding the electrical phenomena occurring. The electrical 

 impulse is the central fact. No chemical, no molecule, travels at the 

 rate of the spike potential — only an electrical disturbance is transmitted. 



4. Clamped Nerve Experiments 



The third simplified system discussed here was used originally by 

 Hodgkin and Huxley on the giant axons of squids and cuttlefish. They 

 used five electrodes, two within the axon and three outside; in this 

 manner, the current to the axon could be electronically controlled to 

 hold the membrane clamped at a potential difference determined by the 

 experimenter. The current passed between electrodes not used for the 

 potential measurements so that polarization effects did not interfere 

 with the action of the electronic clamp. By a suitable electrode arrange- 

 ment, it was also possible to measure the current through a predeter- 

 mined length of axon, across which the potential was essentially constant. 

 Figure 5a is a pictorial sketch of the electrode arrangement, whereas 

 Figure 5b is a schematic cross section. 



The current applied to the membrane is supplied to electrodes a and e . 

 The potential drop across the membrane is measured from b to c, whereas 

 the current through the membrane section studied is measured in terms 

 of the potential drop from c to d. This arrangement results in a relatively 

 long axon membrane all of which will have the same potential drop 

 across it at any given time. The long electrodes and plastic separators 

 also result in all currents in the central compartment (containing 

 electrodes b, c, and d) flowing in the radial direction only. Because the 

 current supplied goes from electrode a to electrode e, these may become 



