Divalent cations modulate TRPV1 activity in cultured dorsal root ganglion neurons

초록

TRPV1 has a key role in the sensation of thermal and inflammatory pain. Transition trace metal ions such as Zn2+, Mn2+, and Co2+ are required cofactors for many essential cellular functions through alteration of function of membrane channels and receptors. In addition, group IIB divalent cations including Zn2+ are known to have potential to oxidize sulfhydryl residues of functional proteins such as ion channels and enzymes. In the present study, we investigated the effects of various divalent cations on TRPV1 activity using patch clamp technique in cultured dorsal root ganglion neurons. Hg2+, Cd2+, and Zn2+ belong to Group IIB decreased capsaicin-activated inward currents reversibly and their effects were reversed by pretreatment of reducing agent, dithiothreitol. These results suggest the decreasing effect of Hg2+ and other group IIB cations may related to the oxidation of extracellular sulfhydryl residues. However, other divalent cations, such as Co2+, Cu2+ and Ba2+ showed diverse effects on TRPV1 activity. These results suggest that the trace elements may play an important role in the regulation of inflammatory pain transmission by regulation of TRPV1 activity.