title: Veratridine modifies open sodium channels.
abstract: The state dependence of Na channel modification by the alkaloid neurotoxin veratridine was investigated with single-channel and whole-cell voltage-clamp recording in neuroblastoma cells. Several tests of whole-cell Na current behavior in the presence of veratridine supported the hypothesis that Na channels must be open in order to undergo modification by the neurotoxin. Modification was use dependent and required depolarizing pulses, the voltage dependence of production of modified channels was similar to that of normal current activation, and prepulses that caused inactivation of normal current had a parallel effect on the generation of modified current. This hypothesis was then examined directly at the single-channel level. Modified channel openings were easily distinguished from normal openings by their smaller current amplitude and longer burst times. The modification event was often seen as a sudden, dramatic reduction of current through an open Na channel and produced a somewhat flickery channel event having a mean lifetime of 1.6 s at an estimated absolute membrane potential of -45 mV (23 degrees C). The modified channel had a slope conductance of 4 pS, which was 20-25% the size of the slope conductance of normal channels with the 300 mM NaCl pipette solution used. Most modified channel openings were initiated by depolarizing pulses, began within the first 10 ms of the depolarizing step, and were closely associated with the prior opening of single normal Na channels, which supports the hypothesis that modification occurs from the normal open state.
authors: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.
authors: S
authors: S
authors: Barnes
authors: B
authors: B
authors: Hille
mesh_terms: D000818:Animals; D004553:Electric Conductivity; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
chemical_list: D007473:Ion Channels; D014701:Veratridine; D012964:Sodium; D014702:Veratrine