Kinetic analysis of pancuronium interaction with sodium channels in squid axon membranes

J. Z. Yeh, Toshio Narahashi

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


The interaction of pancuronium with sodium channels was investigated in squid axons. Sodium current turns on normally but turns off more quickly than the control with pancuronium 0.1-1 mM present internally. The sodium tail current associated with repolarization exhibits an initial hook and then decays more slowly than the control. Pancuronium induces inactivation after the sodium inactivation has been removed by internal perfusion of pronase. Such pancuronium- induced sodium inactivation follows a single exponential time course, suggesting first order kinetics which represents the interaction of the pancuronium molecule with the open sodium channel. The rate constant of association k with the binding site is independent of the membrane potential ranging from 0 to 80 mV, but increases with increasing internal concentration of pancuronium. However, the rate constant of dissociation l is independent of internal concentration of pancuronium but decreases with increasing the membrane potential. The voltage dependence of l is not affected by changing external sodium concentration, suggesting a current-independent conductance block. The steady-state block depends on the membrane potential, being more pronounced with increasing depolarization, and is accounted for in terms of the voltage dependence of l. A kinetic model, based on the experimental observations and the assumption on binding kinetics of pancuronium with the open sodium channel, successfully simulates many features of sodium current in the presence of pancuronium.

Original languageEnglish (US)
Pages (from-to)293-323
Number of pages31
JournalJournal of General Physiology
Issue number3
StatePublished - Mar 1 1977

ASJC Scopus subject areas

  • Physiology


Dive into the research topics of 'Kinetic analysis of pancuronium interaction with sodium channels in squid axon membranes'. Together they form a unique fingerprint.

Cite this