l62 ELECTROLYTES IN BIOLOGICAL SYSTEMS 



anaerobic reserves can be supplemented by glucose^ or blocked by glycolytic 

 inhibitors such as fluoride and iodoacetate; pyruvate and lactate cannot be 

 utilized in the absence of oxygen (53). In other nerves the relative dependence 

 on aerobic or anaerobic processes may be greater or less than in the frog sciatic 



(59). 



c) Return to oxygen, following anoxia, reverses ionic movement at least in 

 the case of potassium (13, 43, 44). The presence of iodoacetate or fluoride 

 during the anoxic period interferes with the recovery. This action of iodoacetate 

 is reversed by either lactate or pyruvate, but that of fluoride is counteracted 

 only by pyruvate (53). These observations suggest that the accumulation of 

 lactate and pyruvate during anoxia provides readily utilized substrate for 

 restoration of the normal electrical and ionic conditions upon return to oxygen, 

 pyruvate oxidation being that most immediately linked with ionic transfer 

 under these conditions. Many of these metabolic relationships have also been 

 demonstrated by biochemical procedures or by measurements of heat produc- 

 tion (11). 



An important aspect of these findings and conclusions is that any interference 

 with metabolism will, in general, lead to degradation in normal ionic distribu- 

 tion and that suitable substrates, utilizable at a level below that of the inhibi- 

 tion, can maintain the ionic balance. The proximity of the reactions to the 

 actual ion transfer or retention machinery cannot be deduced with certainty 

 from such data. This objection must be considered when other so-called 

 'specific' inhibitors and associated substrates are proposed as directly involved 

 in either the bioelectrical phenomena or the ionic interchanges of this and 

 other biological systems. 



Moreover, it must be emphasized that the correlation of depolarization and 

 conduction block with potassium loss in vertebrate nerve which has been util- 

 ized above is a necessary consequence of the past employment for electrical 

 measurements of techniques — the moist chamber and nerves with intact 

 peripheral sheaths (i.e., epineuria) — which permitted the accumulation of the 

 escaping potassium in the interstitial spaces (e.g., 34, 53), where it could pro- 

 duce its familiar effects. Not until precautions are taken to prevent such potas- 

 sium accumulation can a determination be made as to whether the resting and 

 action potentials are affected in any other manner by metabolic changes. 



A significant feature of most of the ionic changes is that both potassium and 

 sodium shifts are of the same magnitude. The question arises as to whether this 

 exchange is an obligatory one resulting from the operation of a single mecha- 

 nism, or whether the transfer of these ions involves separate mechanisms for the 

 two ions but so coupled together under usual experimental conditions as to 



2 A peculiar feature of glucose utilization is that at late times the ionic interchanges are 

 accelerated. The statement by Lorente de No (34) that glucose accelerates anoxic decline is 

 based on observations at late times, which agrees with the analytical data. 



