Effects of hydroxybenzenes on the a-currents in molluscan neurons

1. The relationship between the number and positions of the hydroxy groups on the benzene ring and the effects on the A-current in identified Helix neurons was examined with phenol, hydroquinone, resorcinol, catechol, phloroglucinol and pyrogallol. 2. Qualitative differences were found when the actions of phenol were compared with those of di- or trihydroxybenzenes. 3. Phenol suppressed the amplitude of the A-current similarly to dihydroxybenzenes (ic50 = 5 mM), whereas trihydroxybenzenes were ineffective when they were applied in this concentration (5 mM, 15 min). 4. There was no correlation between the effects of hydroxybenzenes on the A-current amplitude and the calculated octanol/water partition coefficient (log P). 5. Phenol decreased the decay time constant of the A-currents, but dihydroxybenzenes increased it with decreasing potency in the following sequence: hydroquinone > resorcinol > catechol. 6. There was a significant correlation between the effects of the hydroxybenzenes in the decay time constant of the A-current and log P. 7. A structure-activity analysis clearly showed that the benzene ring in combination with at least one OH group is necessary for the recorded events. However, further substituents can highly modulate the effectiveness of the molecule. 8. We suggest that a hydrophobic interaction is responsible for the action of the hydroxybenzenes on the kinetics of the A-current.