CELLULAR AND TISSUE FUNCTION 211 



prevented by oxidizable substrates such as succinate, glutamate, and a- 

 ketoglutarate, and that malonate counteracts this preventive action. These 

 results were confirmed by Kaufman and Kaplan (1960), who again ob- 

 served, in contrast to the earlier workers, that succinate inhibits swelling 

 and malonate reverses this protection. They believe that swelling is correl- 

 ated with the mitochondrial release of pyridine nucleotides (see tabulation). 



Pyridine nucleotide released 

 (//g/20 min) 



Optical density 



No substrate 64 —0.710 



Succinate (20 mM) 14 —0.095 



Malonate (20 mM) 68 -0.740 



Succinate + malonate 38 — 0.520 



Succinate reduces the loss of the pyridine nucleotides and malonate anta- 

 gonizes this effect. One must conclude that there must be different mecha- 

 nisms of swelling and that the mitochondrial behavior perhaps depends on 

 the metabolic state and the nature of the suspension medium. The effects 

 of malonate and other anions on the concentrations of free Ca++ and Mg++ 

 should also not be ignored, inasmuch as EDTA has usually been shown to 

 modify the swelling. 



Conduction and Membrane Potentials of Nerve 



Penetration of malonate into nerve axons in the physiological pH range 

 must be very poor. This may account for the failures of Shanes and Brown 

 (1942) to observe an eft'ect of 20 mM malonate on the resting potential of 

 frog nerve, and of Greengard and Straub (1962) to find an effect of 10 mM 

 malonate on nonmyelinated nerve posttetanic hyperpolarization, despite 

 the fact that this phenomenon is quite sensitive to other inhibitors. How- 

 ever, Jenerick (1957) reported some effect of 10 mM malonate on frog sciatic 

 nerve although the action was presumably slow in developing. When the 

 action potential spike amplitude is reduced by 80-90%, the threshold for 

 stimulation begins to rise rapidly. Conduction block occurs when the rest- 

 ing potential has fallen by 30-40%. It is doubtful if the decrease in external 

 Ca++ concentration, which was 1.3 mM initially, resulting from chelation 

 by malonate could be held responsible for these effects, and it was felt 

 that metabolic interference must occur. The preganglionic and postgan- 

 glionic action potentials in preparations of cat sympathetic ganglia are 

 depressed equally (75-80%) by 14 mM malonate and transmission through 

 the ganglia is reduced (Larrabee and Bronk, 1952). The excitability of the 



