The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro.
The selective excitant and neurotoxic action of capsaicin on vagal sensory neurons in the rat has been investigated in vitro using three techniques: extracellular recording of compound spike potentials from the whole nerve; intracellular recording from ganglion cells using single-electrode current and voltage clamp; and electron microscopy of the nerve and nodose ganglion. Capsaicin (0.1-10 microM) depolarized vagal sensory C fibres and cell bodies, and produced an increased conductance. The conductance increase appeared to be due to an increased permeability to sodium and calcium, plus a secondary increase in potassium (and perhaps chloride) conductance consequent upon calcium entry. The early entry of calcium seems to be a significant priming event in the neurotoxic process, since dramatic ultrastructural changes take place within a few minutes of capsaicin application, which are minimized by removing extracellular calcium ions. The observations indicate that in sensory C neurons capsaicin opens a conductance of limited specificity and that a resultant large calcium entry is closely involved in the rapid development of cell injury.
Marsh
S J
SJ
Department of Pharmacology, School of Pharmacy, University of London, U.K.
Stansfeld
C E
CE
Brown
D A
DA
Davey
R
R
McCarthy
D
D
D000818:Animals; D001369:Axons / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014630:Vagus Nerve / Q000187:drug effects*
D002211:Capsaicin