Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8478600 | Molecular and Cellular Neuroscience | 2014 | 10 Pages |
Abstract
Inflammatory mediators induce neuropeptide release from nociceptive nerve endings and cell bodies, causing increased local blood flow and vascular leakage resulting in edema. Neuropeptide release from sensory neurons depends on an increase in intracellular Ca2Â + concentration. In this study we investigated the role of two types of pH sensors in acid-induced Ca2Â + entry and neuropeptide release from dorsal root ganglion (DRG) neurons. The transient receptor potential vanilloid 1 channel (TRPV1) and acid-sensing ion channels (ASICs) are both H+-activated ion channels present in these neurons, and are therefore potential pH sensors for this process. We demonstrate with in situ hybridization and immunocytochemistry that TRPV1 and several ASIC subunits are co-expressed with neuropeptides in DRG neurons. The activation of ASICs and of TRPV1 led to an increase in intracellular Ca2Â + concentration. While TRPV1 has a high Ca2Â + permeability and allows direct Ca2Â + entry when activated, we show here that ASICs of DRG neurons mediate Ca2Â + entry mostly by depolarization-induced activation of voltage-gated Ca2Â + channels and only to a small extent via the pore of Ca2Â +-permeable ASICs. Extracellular acidification led to the release of the neuropeptide calcitonin gene-related peptide from DRG neurons. The pH dependence and the pharmacological profile indicated that TRPV1, but not ASICs, induced neuropeptide secretion. In conclusion, this study shows that although both TRPV1 and ASICs mediate Ca2Â + influx, TRPV1 is the principal sensor for acid-induced neuropeptide secretion from sensory neurons.
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Authors
Aurélien Boillat, Omar Alijevic, Stephan Kellenberger,