Local anesthetic block of sodium channels in normal and pronase-treated squid giant axons

Biophys J. 1978 Aug;23(2):285-311. doi: 10.1016/S0006-3495(78)85449-6.


The inhibition of sodium currents by local anesthetics and other blocking compounds was studied in perfused, voltage-clamped segments of squid giant axon. When applied internally, each of the eight compounds studied results in accumulating "use-depnedent" block of sodium currents upon repetitive pulsing. Recovery from block occurs over a time scale of many seconds. In axons treated with pronase to completely eliminate sodium inactivation, six of the compounds induce a time- and voltage-dependent decline of sodium currents after activation during a maintained depolarization. Four of the time-dependent blocking compounds--procaine, 9-aminoacridine, N-methylstrychnine, and QX572--also induce altered sodium tail currents by hindering closure of the activation gating mechanism. Treatment of the axon with pronase abolishes use-dependent block completely by QX222, QX314, 9-aminoacridine, and N-methylstrychnine, but only partially be tetracaine and etidocaine. Two pulse experiments reveal that recovery from block by 9-aminoacridine or N-methyl-strychnine is greatly accelerated after pronase treatment. Pronase treatment abolishes both use-dependent and voltage-dependent block by QX222 and QX314. These results provide support for a direct role of the inactivation gating mechanism in producing the long-lasting use-dependent inhibition brought about by local anesthetic compounds.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acridines / pharmacology
  • Anesthetics, Local / pharmacology*
  • Animals
  • Axons / drug effects*
  • Axons / metabolism
  • Etidocaine / pharmacology
  • Lidocaine / analogs & derivatives
  • Lidocaine / pharmacology
  • Membrane Potentials / drug effects
  • Procaine / pharmacology
  • Pronase / pharmacology
  • Sodium / metabolism*
  • Strychnine / analogs & derivatives
  • Strychnine / pharmacology
  • Tetracaine / pharmacology


  • Acridines
  • Anesthetics, Local
  • Tetracaine
  • N-methylstrychnine
  • Procaine
  • Lidocaine
  • Sodium
  • Pronase
  • Strychnine
  • Etidocaine