Potentiation of ASIC currents by lysophosphatidic acid in rat dorsal root ganglion neurons

Abstract

Lysophosphatidic acid (LPA) is a phospholipid which has been implicated in pain. Acid‐sensing ion channels (ASICs) are important players in pain associated with tissue acidification. However, it is still unclear whether there is a link between LPA signaling and ASICs in pain processes. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pre‐application of LPA enhanced ASIC‐mediated and acid‐evoked inward currents in a concentration‐dependent manner. LPA shifted the concentration–response curve for protons upwards, with an increase of 41.79 ± 4.71% in the maximal current response of ASICs to protons in the presence of LPA. Potentiation of ASIC currents by LPA was blocked by the LPA1 receptor antagonist Ki16198, but not by the LPA2 receptor antagonist H2L5185303. The LPA‐induced potentiation was also prevented by intracellular application of either G protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. LPA also enhanced ASIC3 currents in CHO cells co‐expressing ASIC3 and LPA1 receptors, but not in cells expressing ASIC3 alone. Moreover, LPA increased the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, LPA exacerbated acid‐induced nociceptive behaviors in rats. These results suggested that LPA enhanced ASIC‐mediated electrophysiological activity and nociception via a LPA1 receptor and its downstream PKC rather than Rho signaling pathway, which provided a novel peripheral mechanism underlying the sensitization of pain.

Acid-Sensing Ion Channels’ Immunoreactivity in Nerve Profiles and Glomus Cells of the Human Carotid Body

“…Nevertheless, the presence of ASIC proteins in the human petrosal ganglion neurons is reported here for the first time. In addition, there is ample functional, physiological, and pharmacological evidence for the presence of all ASIC subunits in rat and mouse spinal ganglia [38][39][40][41]. Thus, the present results suggest that the sensory neurons of the human petrosal ganglion can detect wide ranges of drops in pH, and therefore acidosis, since it expresses all ASIC subunits.…”

Group II metabotropic glutamate receptor activation attenuates acid-sensing ion channel currents in rat primary sensory neurons

“…Electrophysiological experiments were performed as described ( 55 ). A MultiClamp-700B amplifier and Digidata-1440A A/D converter (Axon Instruments) were used for the whole-cell patch clamp recordings.…”