86 MARTIN G. LARRABEE AND PAUL HOROWTCZ 



Although a species was thus found in which resting metabolism of ganglia 

 was disturbed by significantly low concentrations of soriie agents, a number of 

 reasons suggested caution in concluding that the metabolic changes were neces- 

 sarily the cause of the loss of function. One reason was that still greater meta- 

 bolic changes than these could be caused by a substance such as azide, at least 

 in the rate of oxygen consumption, without blocking transmission. Secondly, 

 even in the rat, one circumstance was found where transmission was slightly 

 but significantly impaired without change in uptake either of oxygen or of 

 glucose; this was during the application of 0.5 mM chloretone. In another case, 

 that of ether, oxygen uptake was not significantly changed even with 50% block 

 of transmission; possible effects of this agent on glucose uptake have not yet 

 been studied. Finally, the marked contrast between ganglia from rats and rab- 

 bits suggests that the coincidence of functional and metabolic changes, found 

 only in rats, may not signify a causal relation, but may merely indicate that in 

 this species two independent effects happen to be produced in the same range 

 of concentrations. These results thus yield no compelling evidence that the 

 basis of anesthetic action lies in effects on the resting component of metabolism^ 



Anesthetics on Metabolism in Active Ganglia 



Several lines of evidence indicate that conduction and discharge of nerve 

 impulses are associated with some chemical reactions which occur at a much 

 slower rate or not at all in resting neurons. We have recently found, for example, 

 that significant amounts of endogenous substrates are oxidized during activity 

 in excised sympathetic ganglia, whereas the oxygen consumed at rest can be 

 almost entirely accounted for by oxidation of exogenous glucose. (See Part II 

 of this paper.) These findings are in agreement with observations of others on 

 peripheral nerve trunks (Holmes et al., 1930; Mullins, 1953). Moreover it has 

 been reported that the activity increment in oxygen consumption by nerves 

 and muscles of frogs is depressed by lower concentrations of azide than is the 

 resting rate of oxygen uptake; this may also be interpreted by assuming that 

 different reactions are involved in the activity and resting components of 

 metabolism (Brink et al., 1952; Doty and Gerard, 1950; Stannard, 1939). 



It is therefore possible that an anesthetic, in appropriate concentrations, 

 might interfere with chemical reactions which are of importance only during 

 activity. This might explain, for example, why oxygen consumption is more 

 readily depressed by anesthetics when tissues are submitted to appropriate 

 electrical stimulation than when no such stimulation is applied. This has been 

 observed in frog nerve (Brink et al, 1952), in mammalian sympathetic ganglia 

 (Larrabee, Ramos and Biilbring, 1952), and in slices of cerebral cortex (Mcll- 

 wain, 1953). It might also explain why electrical responses to repetitive excita- 

 tion are more affected by a given concentration of anesthetic than is the response 

 to a single stimulus in ganglia (Larrabee and Posternak, 1952), and brain (Forbes 



