Low pH facilitates capsaicin responses in isolated sensory neurons of the rat

Abstract

The effects of capsaicin (CAPS; 30 nM, 300 nM, 3 microM) and acidic solutions (pH 6.6, 6.1, 5.6, 5.1) were studied in dorsal root ganglion (DRG) neurons from adult rats in short term culture using the whole cell patch-clamp technique and a system for fast drug application. At -60 mV holding potential, both CAPS 30 nM and 300 nM for 10 s did not induce a significant membrane current in pH 7.3. The first response to 3 microM CAPS at pH 7.3 yielded an inward current of 898 +/- 517 pA and with pH 6.1 the sustained proton-induced current was 365 +/- 153 pA. A more than additive current increase was observed when both agents were applied together even at subthreshold concentrations of CAPS or protons. Similar results were obtained at positive holding potential. Facilitation was also observed when extracellular pH 6.1 solution was applied immediately after discontinuation of 3 microM CAPS application but not when CAPS followed the application of pH 6.1 solution (n = 8). The proton-induced current as well as the CAPS-pH response both increased with proton concentration and showed the same short relaxation time relative to the CAPS response. The facilitation saturated near pH 5.6, and was present in repeated trials when responses to CAPS were markedly decreased due to tachyphylaxis. It is suggested that protonation of CAPS gated ion channels increases their open probability or conductance and modulates their kinetics.