Modulation by alkyl p-hydroxybenzoates of voltage- and ligand-gated channels in peripheral neuronal cells

Effects of alkyl p-hydroxybenzoates (APHBs), which are used as preservatives, on ion channels were investigated in rat pheochromocytoma PC12 cells. Methyl p-hydroxybenzoate (MPHB; 300 microM) and butyl p-hydroxybenzoate (BPHB; 300 microM) inhibited Ba2+ current passing through Ca2+ channels, and facilitated the inactivation of the Ba2+ current. K+ current obtained with a depolarizing voltage-step was also suppressed by 300 microM MPHB or 300 microM BPHB. The extent of the suppression of the K+ current was not affected by extracellular Cd2+, suggesting that the suppression of the K+ current is not a secondary effect arising from the Ca2+ channel inhibition. An inward current activated by acetylcholine (ACh; 100 microM) was abolished by 300 microM BPHB, and it was partially blocked by 300 microM MPHB. In contrast to the ACh-activated current, an inward current activated by ATP (30 microM) was markedly potentiated by 300 microM BPHB. The results suggest that APHBs exert significant effects on the voltage- and ligand-gated channels. The significance of these channel modifications were discussed in relation to reported effects of APHBs, including induction of minor irritation.