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)