Ionic mechanism of the salicylate block of nerve conduction.
Benzoic acid, salicylic acid and 5-bromosalicylic acid have been studied for their mechanism of action on crayfish and squid giant axons. External application of 0.1 to 0.5 mM 5-bromosalicylic acid prolonged the falling phase of the action potential, and at concentrations higher than 1.5 mM, nervous conduction was blocked. Boltage clamp analyses showed that 5-bromosalicylic acid reduced both peak transient sodium conductance and steady-state potassium conductance. The curves relating the peak and steady-state conductances to membrane potential were shifted in the direction of depolarization. The time constant for the activation of sodium current (taum) was not affected by 5-bromosalicylic acid, whereas the time constant for the sodium inactivation (tauh) was greatly increased. The steady-state sodium inactivation curve (h infinity) was shifted in the hyperpolarizing direction. The rate constants alpha h and beta h were decreased. The rate of activation of potassium current was reduced. The block of peak transient conductance by externally applied 5-bromosalicylic acid was largely reversed by internal washing suggesting that the drug acts on a membrane site more easily accessible from inside than from outside. Salicylic and benzoic acids were much less potent than 5-bromosalicylic acid, reducing peak conductance by 12.5 and 3%, and steady-state conductance by 8.7 and 7%, respectively, at a concentration of 10 mM.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000502:physiology; D001565:Benzoates / Q000494:pharmacology; D049832:Decapodiformes; D004553:Electric Conductivity; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects*; D009994:Osmolar Concentration; D011188:Potassium / Q000502:physiology; D012459:Salicylates / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology; D013997:Time Factors
D001565:Benzoates; D012459:Salicylates; D012964:Sodium; D011188:Potassium