THE EFFECT OF FLUOROACETATE ON THE SARTORIUS MUSCLE OF THE FROG

¹ Department of Pharmacology, Cornell University Medical College, New York City

Fluoroacetate (FA) causes a progressive decrease in the contractility of the frog sartorius muscle. Although complete fatigue may occur, contracture never develops. The gradual failure of the muscle is related to an impairment of the recovery processes. This is reflected by the absence of aerobic recovery heat production in the electrically stimulated muscle. It is noteworthy that iodo- or bromacetate exerts a similar though lesser effect on recovery heat production.

The effect of FA on the resting oxidations of frog muscle is minimal. However, exposure of the muscle to FA prior to its chemical stimulation by caffeine prevents to a considerable extent the extra oxygen consumption associated with activity. Others have shown a similar action for brom- and iodoacetate and it is probable that this effect is independent of their characteristic inhibition of glycolysis. However, this effect is most evident with FA and supports the conclusion that the restoration of the potential energy of the system depends on the concurrent oxidative processes.

The inhibition by FA of the activity oxygen consumption of frog muscle can be averted by the addition of the following substrates: sodium pyruvate, sodium acetate, sodium propionate and mono-, di-, and triacetin. It is assumed that these substances provide the muscle with a utilizable source of energy.

The characteristic inhibitory action of iodo- and bromacetate on anaerobic glycolysis is not evidenced by FA. Indeed, the rate of anaerobic glycolysis is increased in the presence of FA. Measurement of aerobic lactate formation by the continuously stimulated and unpoisoned muscle reveals that a moderate concentration accumulates in the bath fluid. In contrast, there is no accumulation of lactate in the fluid bathing the continuously stimulated muscle poisoned with FA.

The results presented support the hypothesis that FA interferes with the utilization of pyruvate. It is probable that FA and pyruvate (or suitable precursors) compete for entry into the pathway of pyruvate oxidation.