Procaine actions on tetrodotoxin sensitive and insensitive leech neurons.

Procaine (0.1-10 mM) was applied to two kinds of identified neurons in segmental leech ganglia. Both Retzius (R) cells and nociceptive (N) cells responded by dose-dependent reduction of maximum rates of de- and repolarization during action potentials. However, the N cells, which are more sensitive to tetrodotoxin than R cells, were also 3 times more sensitive to procaine. The prolongation of action potentials produced by procaine in R cells was enhanced by low Ca but antagonized by high Ca. This implies that the drug interfered with repolarization by affecting a Ca-dependent mechanism. In alkaline solution (pH 8.5), sensitivity of the R cell to procaine approached that of the N cell at pH 7.4 suggesting that the drug acted at an intracellular site after passage through membrane lipids in its uncharged form. The combined effects of TTX and procaine, in concentrations which produced about 50% inhibition of dV/dTdep in N cells when given separately, were found to be intermediate between those predicted by two models which assume identical and independent sites of action, respectively. These data extend our earlier observations regarding the existence of two types of Na channels in mature leech neurons. They imply that the differential sensitivity to procaine among these cells may be a consequence of variable access to an otherwise identical 'receptor' and that TTX and procaine act on separate sites which may interact with each other.