An interaction of inflammatory mediators and protons in small diameter dorsal root ganglion neurons of the rat.

The effects of inflammatory mediators (bradykinin, serotonin, prostaglandin E2 and histamine) and of acidic solutions on dissociated sensory neurons from the adult rat were studied using the whole cell patch-clamp technique and a fast system for drug application. At -60 mV holding potential, a large subpopulation of small neurons responded to acidic pH (6.1) with a sustained inward current whereas none of the inflammatory mediators induced a sustained excitatory conductance. In 3/17 pH-sensitive neurons, a small 130 pA inward current was observed in response to serotonin that exhibited fast inactivation. Addition of 10(-5) M serotonin, prostaglandin E2 or histamine singly did not alter the sustained proton-induced current. However, addition of bradykinin (10(-5) M) resulted in a significant increase of the current which was even more facilitated when all the inflammatory mediators were applied together at pH 6.1. We suggest that inflammatory mediators may act to modulate ionic channels, that are operated by protons, possibly via intracellular second messenger action.