FAST AXOPLASMIC TRANSPORT IN MAMMALIAN NERVE IN VITRO AFTER BLOCK OF GLYCOLYSIS WITH IODOACETIC ACID

Abstract— Fast axoplasmic transport of components incorporating L-[³H]leucine in cat sciatic nerve occurred in vitro at a rate of 407 ± 21 (S.D.) mm/day. Although fast transport had earlier been shown to be blocked within 10 to 15 min by asphyxiation with nitrogen or by agents such as NaCN or dinitrophenol that interfere with oxidative phosphorylation, interruption of glycolysis by application of iodoacetate resulted in a gradually diminishing transport with a complete block in about 2 h. This block characteristically showed a sloping front instead of the usual crest of activity found in the nerve after the 3 h period usually allowed for in vitro downflow. The declining slope of radioactivity in the nerve seen after exposure to iodoacetate was not the result of a delayed entry of iodoacetate into the nerve fibres. We consider it to be the consequence of a limited and diminishing supply of endogenous metabolites entering the tricarboxylic acid cycle below the site of glycolytic block by iodoacetate. When either pyruvate or L-lactate was supplied to the iodoacetate-blocked nerve, recovery of the normal pattern and distance of flow was effected. Pyruvate partially reversed the iodoacetate block at concentrations as low as 2 mM, with almost complete recovery at approximately 25 mM. A concentration of L-lactate approx. 20 times that of pyruvate was required for a comparable degree of reversal of iodoacetate block.