Differential sensitivity of tetrodotoxin of nociceptive neurons in 4 species of leeches.
We have recently shown that the nociceptive neurons (N cells) in the leech can be segregated into a medial type (Nmed) and a lateral type (Nlat) according to their physiological and pharmacological properties. We now report that the Na-dependent action potential (AP) of the 2 cell types in Macrobdella have differential sensitivities to tetrodotoxin and that the APs of the N-cell homologs from different leech species also vary considerably in their response to TTX. The normal AP of the N cells in the 4 leech species was exclusively Na-dependent; its overshoot varied logarithmically with [Na]0, was unaffected by the presence of Mn and absence of Ca, and could not be elicited in Na-free Ringer's solutions. The decrease in the maximal rate of depolarization (Vmax) of the Na-dependent AP of the Nmed cell in Macrobdella produced by TTX followed a reverse Langmuir curve for bimolecular reaction with an ED50 of 9 microM. Almost complete blockage was obtained at 50 microM. In contrast, TTX inhibition of Vmax in the Nlat cell reached saturation at a level of only 55% reduction in Vmax even at doses in excess of 200 microM TTX. The simplest interpretation of these data is that there are 2 types of Na channels in the Nlat cell. This is further supported by the fact that the dose-response data could be well fitted by a Langmuir curve, assuming that the Nlat cell possesses 2 populations of Na conductances--one insensitive to TTX and one (like the Nmed cell) with an ED50 to TTX of 9 microM, the 2 populations being present in a 0.45:0.55 ratio, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D007473:Ion Channels / Q000502:physiology; D007700:Kinetics; D007865:Leeches / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009619:Nociceptors / Q000166:cytology / Q000502:physiology*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D013045:Species Specificity; D013779:Tetrodotoxin / Q000494:pharmacology*
D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium