Guaiacol and vanilloid compounds modulate the A-type potassium currents in molluscan neurons

The actions of guaiacol (2-methoxy-phenol), vanillin (4-hydroxy-3-methoxy-benzaldehyd) and other vanilloid compounds such as zingerone (4-/4-hydroxy-3-methoxyphenyl/-2-butanon) and eugenol(2-methoxy4-/2-propenyl/phenol) were investigated on the fast outward potassium currents (A-type currents) in molluscan neurons. Guaiacol (0.01-0.1%, w/v) moderately decreased the peak amplitude but increased the rate of inactivation of the A-currents in dose-dependent way (Kd = 0.06% 4 mM, nH = 0.8). Vanillin (5 mM) slightly decreased the peak amplitude of the A-currents in Helix neurons but its action was more pronounced in dialysed Lymnaea nerve cells. However, vanillin similarly decreased the time-to-peak and the time constant of decay of the A-currents both in the faster and the slower inactivating Lymnaea and Helix neurons (Kd = 5 mM, nH = 0.6). The voltage-dependence of activation and inactivation of the A-currents were not significantly influenced by guaiacol and vanillin in Helix or Lymnaea neurons. Vanillin hardly influenced the delayed outward currents, but decreased the leak currents in the identified LPa and RPa 2,3 neurons. A structure-activity analysis clearly showed that increasing alkyl tail length from the aldehyde side of the vanillin molecule increased the efficacy of the various compounds on the amplitude of the A-currents and modified the kinetical influence on the A-current channel. Furthermore, an attenuation of the late outward currents and an increase of the leak conductance also developed in the presence of zingerone or eugenol. Excitatory actions of the studied vanilloids predominated on the various molluscan neurons.