Alkaline pH causes pain sensation through TRPA1 activation

Abstract

Living things survive in a very narrow range of pH, and possess physiological detection and defense mechanisms when ambient pH becomes out of the narrow range. Regarding pain sensation evoked by exposure to acidic pH, sensory neurons sense the reduction in pH by specific ion channels such as TRPV1 and ASIC. Here we show that alkaline pH activates TRPA1 ion channel, which belongs to the TRP super family and is involved in nociception, using calcium-imaging and patch-clamp methods. Furthermore, it became clear that increase in the intracellular, but not extracellular pH causes TRPA1 activation, in the experiment where ammonium chloride with pH7.4 was used, which causes intracellular alkalization. Activation of TRPA1 by intracellular alkalization was supported by the single-channel recordings in outside/out excised membrane patches. In addition, alkaline solution-evoked whole-cell currents exhibit similar electrophysiological properties to those observed in HEK293 cells expressing TRPA1 in response to AITC application. [J Physiol Sci. 2008;58 Suppl:S164]