TRPC channels and diacylglycerol dependent calcium signaling in rat sensory neurons

Abstract

Transient receptor potential (TRP) channels of the TRPV, TRPA, and TRPM subfamilies play important roles in somatosensation including nociception. While particularly the Thermo TRPs have been extensively investigated in sensory neurons, the relevance of the subclass of "canonical" TRPC channels in primary afferents is yet elusive. In the present study, we investigated the presence and contribution to Ca(2+) transients of TRPC channels in dorsal root ganglion neurons. We found that six of the seven known TRPC subtypes were expressed in lumbar DRG, with TRPC1, C3, and C6 being the most abundant. Microfluorimetric calcium measurements showed Ca(2+) influx induced by oleylacylglycerol (OAG), an activator of the TRPC3/C6/C7 subgroup. Furthermore, OAG induced rises in [Ca(2+)](i) were inhibited by SKF96365, an inhibitor of receptor and store operated calcium channel. OAG induced calcium transients were also inhibited by blockers of diacylglycerol (DAG) lipase, lipoxygenase or cyclooxygenase and, intriguingly, by inhibitors of the capsaicin receptor TRPV1. Notably, SKF96365 did not affect capsaicin-induced calcium transients. Taken together, our findings suggest that TRPC are functionally expressed in subpopulations of DRG neurons. These channels, along with TRPV1, contribute to calcium homeostasis in rat sensory neurons.

TRPC3: A New Target for Therapeutic Strategies in Chronic Pain−DAG-mediated Activation of Non-selective Cation Currents and Chronic Pain (Mol Pain 2014;10:43)

“…From Alkhani et al, 11 it is more evident that DAG is a real trigger to prolong intracellular calcium elevation contributing to sensitization of nociceptors and chronic pain in inflammatory conditions. There are the following evidences to support their claims: first, TRPC3 is physically expressed in small and medium diameter sensory neurons that are for responsible to pain, this is consistent with an earlier study reported by Kress et al 13 Second, these neurons evoked a significant increase of Gd…”

“…Furthermore, activation of P2Y2 purinoceptors (P2Y2 receptor) or PAR2 triggered a strong increase in intracellular calcium which is attributed from TRPC3 overexpression; on other hand, it was suppressed in knockdown of native TRPC3 and suppressed by Pyr10. Authors in this study and other studies 13 have also found that TRPC1 is present in DRG sensory neuron, including small and medium sized neurons. TRPC1 function has also been linked to ubiquitous stromal interaction molecule 1 (STIM1)-dependent SOCE.…”

Signaling mechanisms involved in the intestinal pro-secretory actions of hydrogen sulfide

“…It is unlikely that SKF96365 directly interacts with TRPV1 because the capsaicin evoked calcium transients were not affected by SKF96365. 39 Strikingly, 2-APB reduced NaHS evoked secretion at a 100 fold lower concentration than usually required to block IP3 mediated calcium release in other tissue or cell systems. 40 At such low concentrations 2-APB has been shown to block TRPC channels.…”

Excitation and Modulation of TRPA1, TRPV1, and TRPM8 Channel-expressing Sensory Neurons by the Pruritogen Chloroquine

“…Several subtypes are abundantly expressed in DRG neurons (27). To determine the role of TRPC channels in TRPA1-independent excitation of DRG neurons caused by CQ, DRG neurons were treated with the general TRPC channel inhibitor BTP2.…”