Abstract

The effects of various concentrations of iodoacetate have been determined on the isolated rabbit auricle. Sinus rate and contractility were the functions most sensitive to iodoacetate inhibition. Electrical excitability and the action potential were less affected, and the refractory period and conduction velocity, were practically unchanged at a time when rate and contractility had been markedly inhibited. The effects of temperature, pH of the medium, rate of stimulation and concentration of IOA on the speed of action of iodoacetate have been determined.

The effects of substrates such as acetate, pyruvate, lactate, and butyrate have also been demonstrated. Auricles poisoned by low doses of iodoacetate (4 x 10^-5M) responded by partial recovery to the addition of these substrates. When higher concentrations of IOA are used (8-16 x 10^-5M) and following prolonged exposure these substrates produced minimal or no recovery.

The addition of acetate prior to the administration of IOA resulted in a complete protection of spontaneous rate and partial protection of contractility. The chronotropic action of epinephrine was reduced by all concentrations of IOA studied. With low concentrations of iodoacetate (4 x 10^-5M) this effect of epinephrine could be restored to normal levels by the addition of acetate, pyruvate or lactate. Higher concentrations of IOA reduced both chronotropic and inotropic effects of epinephrine even following the addition of acetate. The results obtained have been discussed and it is concluded that iodoacetate, besides its action on anaerobic glycolysis must have an action on the aerobic energy producing mechanisms.