Calcium entry via TRPV1 but not ASICs induces neuropeptide release from sensory neurons

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Title
Calcium entry via TRPV1 but not ASICs induces neuropeptide release from sensory neurons
Journal
Molecular and Cellular Neuroscience
Author(s)
Boillat A., Alijevic O., Kellenberger S.
ISSN
1044-7431
Publication state
Published
Issued date
04/2014
Peer-reviewed
Oui
Volume
61
Pages
13-22
Language
english
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 Ca2+ concentration. In this study we investigated the role of two types of pH sensors in acid-induced Ca2+ 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. Activation of ASICs and of TRPV1 led to an increase in intracellular Ca2+ concentration. While TRPV1 has a high Ca2+ permeability and allows direct Ca2+ entry when activated, we show here that ASICs of DRG neurons mediate Ca2+ entry mostly by depolarization-induced activation of voltage-gated Ca2+ channels and only to a small extent via the pore of Ca2+-permeable ASICs. Extracellular acidification led to 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 Ca2+ influx, TRPV1 is the principal sensor for acid-induced neuropeptide secretion from sensory neurons.
Keywords
ASIC, calcitonin gene-related peptide, calcium, proton, sensory neuron, substance P, TRPV1
Pubmed
Web of science
Create date
07/05/2014 13:52
Last modification date
17/09/2020 8:22
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