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 μM) and butyul p-hydroxybenzoate (BPHB; 300 μM) 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 μM MPHB or 300 μM 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 μM) was abolished by 300 μM BPHB, and it was partially blocked by 300 μM MPHB. In contrast to the ACh-activated current, an inward current activated by ATP (30 μM) was markedly potentiated by 300 μM 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.