EFFECTS ON NERVE FUNCTION 229 



(Chang and Gerard, 1933). Like muscle contraction, nerve function fails 

 quite rapidly when anoxic conditions are superimposed on the iodoacetate 

 inhibition, whereas either alone requires long periods to depress, indicating 

 again that glycolysis is probably the principal source of energy anaerobic- 

 ally (Ronzoni, 1931). The creatine-P is reduced by iodoacetate (Gerard and 

 Tupikow, 1931; Chang and Gerard, 1933; Holmes, 1933) and more rapidly 

 if the tissue is deprived of oxygen. It is interesting that Dahl et al. (1962) 

 reported iodoacetate at 20 mM to reduce the electrical activity in chicken 

 vagus but to have no effect on creatine-P or ATP levels, even though the 

 nerve is stimulated; the periods of observation here were quite brief. Thi- 

 amine has been reported to fall in stimulated frog nerve poisoned with 

 iodoacetate (Wyss and Wyss, 1945). Lactate can be utilized by iodoacetate- 

 treated nerve, as^ shown by respiration studies (Chang and Gerard, 1933) 

 and by its ability to prolong nerve function (Feng, 1932). Glucose utiliza- 

 tion, however, is markedly decreased as expected, as shown in the perfused 

 frog spinal cord, in which case the R.Q. is reduced from 0.89 to 0.71, res- 

 piration being simultaneously depressed (von Ledebur, 1932 a). The respi- 

 ration of minced rat cortex is depressed by iodoacetate, newborn rats show- 

 ing a greater sensitivity (46% inhibition) compared to adult rats (26% in- 

 hibition) (Tyler, 1942). The endogenous formation of ammonia by brain 

 slices is depressed 42% by 1 mM iodoacetate (Weil-Malherbe and Green, 

 1955 a), in contrast to muscle where iodoacetate increases ammonia release, 

 but the origin of the ammonia is different in the two situations. Finally, 

 the interesting results of Heald (1953) on electrically stimulated brain slices 

 must be considered. The respiration and glycolysis in stimulated tissue are 

 about double that of resting tissue. The resting respiration and glycolysis 

 are rather insensitive to iodoacetate, whereas the activity metabolism is 

 very sensitive, being almost abolished by concentrations of 0.01-0.03 mM 

 (see Fig. 1-10). If in vitro studies with inhibitors are to be applied to in 

 vivo results, these data show that active tissue should be used. In summary, 

 one can conclude that nerve behaves much like muscle in the presence of 

 iodoacetate metabolically, and one would predict nerve function to be in- 

 dependent of lactate formation, but eventually dependent on the energy 

 derived from the oxidation of pyruvate and the stores of ATP and crea- 

 tine-P. 



Inhibition of conduction in nerve axons presents special problems. First, 

 ion pumps have established high ionic gradients for Na+ and K+ across the 

 membrane and, even though these active transports are blocked, the nerve 

 will conduct for some time due to the fact that only a very small fraction 

 of the cell K+ is lost or Na+ from the medium is gained per impulse. Thus 

 the nerve can operate for extended periods even though no energy is im- 

 mediately available. Second, the myelin sheath around most nerves which 

 have been studied presents a barrier to penetration of ionic inhibitors, so 



