A preferential inhibition of impulses in C-fibers of the rabbit vagus nerve by veratridine, an activator of sodium channels.
In seeking a means to reverse local anesthetic block of peripheral nerve, we examined the actions of veratridine (VTD), an agent known to antagonize competitively the binding of local anesthetics to Na channels. The actions of VTD, a steroidal alkaloid "activator" of voltage-gated Na channels, were studied in the rabbit vagus nerve by two methods. In one, the effects of VTD on compound action potentials (APc) propagating through a "veratrinized" segment (11-mm) of nerve were measured by extracellular recording. Single volleys of impulses were unaffected by VTD, but trains of impulses, triggered by repetitive stimulation, were selectively diminished. This "use-dependent" reduction was greatest for the C-fiber component of the APc, less for B-fibers, and inconsequential for A-fibers. Use-dependent inhibition was enhanced by higher stimulation frequency and by increased VTD concentration, and reversed rapidly when stimulation ceased. If the nerve sheath remained intact, the rate of VTD action was far less than in desheathed nerves, but the effects were the same. In the other experimental system, membrane potentials were measured in the veratrinized region of the nerve by a sucrose-gap method. Repetitive stimulation, particularly of C-fibers, produced a cumulative VTD-induced depolarization (VID) that was sustained over several seconds and during which the C-fiber APc was selectively reduced. We propose that this local, use-dependent VID provides the means to inhibit impulses propagating through the veratrinized region. The preferential effect of VTD on C-fibers suggests its possibilities as a relatively selective agent for block of impulse trains in nociceptive afferents.
Schneider
M
M
Anesthesia Research Laboratories, Harvard Medical School, Boston, Massachusetts.
Datta
S
S
Strichartz
G
G
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D008297:Male; D009407:Nerve Block; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D015222:Sodium Channels / Q000187:drug effects*; D013268:Stimulation, Chemical; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D014701:Veratridine / Q000494:pharmacology*
D000779:Anesthetics, Local; D015222:Sodium Channels; D014701:Veratridine