THE ionic pores of nerve membranes have voltage-sensitive gates which control not only ion movements through the pores, but also the access of various drugs to receptors or blocking sites within the pores. One blocking agent with a gate-protected receptor is the quaternary nitrogen compound pancuronium. As shown by Yeh and Narahashi1, it can enter and block sodium pores when applied internally, but it can only equilibrate with its receptor if the pore is activated. Equilibration requires an appreciable fraction of a millisecond, so that pores allow passage transiently before they are blocked. Once in an open pore, a pancuronium ion has a 'foot in the door' action and prevents closing of both the activation and inactivation gate of the pore for as long as it remains in its blocking site. Yeh and Narahashi made their observations by studying ionic current through sodium pores. It is also possible to obtain information about sodium channel gates by measuring gating current, which is a small current generated by movement within the membrane of the charged structures that open and close the pores2. We carried out the studies reported here to ascertain whether pancuronium had the effect on gating current that would be anticipated from its action on INa, and we report here that it does. 'On' gating current, which occurs as the channels are opening and before pancuronium enters, is unaffected, whereas 'off' gating current is slowed by the 'foot in the door' effect, and consequently reduced in amplitude. Our results provide additional evidence that gating current is in fact associated with gating of the sodium pores. Also, they provide a good clue to the nature of that component of the gating current which does not inactivate.
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