scholarly journals Correction: Citral Sensing by Transient Receptor Potential Channels in Dorsal Root Ganglion Neurons

Author(s):  
Stephanie C. Stotz ◽  
Joris Vriens ◽  
Derek Martyn ◽  
Jon Clardy ◽  
David E. Clapham
2010 ◽  
Vol 113 (4) ◽  
pp. 833-844 ◽  
Author(s):  
Peter J. Wickley ◽  
Ryo Yuge ◽  
Mary S. Russell ◽  
Hongyu Zhang ◽  
Michael A. Sulak ◽  
...  

Background The activity of transient receptor potential vanilloid subtype-1 (TRPV1) receptors, key nociceptive transducers in dorsal root ganglion sensory neurons, is enhanced by protein kinase C epsilon (PKCepsilon) activation. The intravenous anesthetic propofol has been shown to activate PKCepsilon. Our objectives were to examine whether propofol modulates TRPV1 function in dorsal root ganglion neurons via activation of PKCepsilon. Methods Lumbar dorsal root ganglion neurons from wild-type and PKC& epsilon;-null mice were isolated and cultured for 24 h. Intracellular free Ca concentration was measured in neurons by using fura-2 acetoxymethyl ester. The duration of pain-associated behaviors was also assessed. Phosphorylation of PKCepsilon and TRPV1 and the cellular translocation of PKCepsilon from cytosol to membrane compartments were assessed by immunoblot analysis. Results In wild-type neurons, repeated stimulation with capsaicin (100 nm) progressively decreased the transient rise in intracellular free Ca concentration. After desensitization, exposure to propofol rescued the Ca response. The resensitizing effect of propofol was absent in neurons obtained from PKCepsilon-null mice. Moreover, the capsaicin-induced desensitization of TRPV1 was markedly attenuated in the presence of propofol in neurons from wild-type mice but not in neurons from PKCepsilon-null mice. Propofol also prolonged the duration of agonist-induced pain associated behaviors in wild-type mice. In addition, propofol increased phosphorylation of PKCepsilon as well as TRPV1 and stimulated translocation of PKCepsilon from cytosolic to membrane fraction. Discussion Our results indicate that propofol modulates TRPV1 sensitivity to capsaicin and that this most likely occurs through a PKCepsilon-mediated phosphorylation of TRPV1.


2016 ◽  
Vol 215 (3) ◽  
pp. 369-381 ◽  
Author(s):  
Shujiang Shang ◽  
Feipeng Zhu ◽  
Bin Liu ◽  
Zuying Chai ◽  
Qihui Wu ◽  
...  

Transient receptor potential A1 (TRPA1) is a nonselective cation channel implicated in thermosensation and inflammatory pain. In this study, we show that TRPA1 (activated by allyl isothiocyanate, acrolein, and 4-hydroxynonenal) elevates the intracellular Ca2+ concentration ([Ca2+]i) in dorsal root ganglion (DRG) neurons in the presence and absence of extracellular Ca2+. Pharmacological and immunocytochemical analyses revealed the presence of TRPA1 channels both on the plasma membrane and in endolysosomes. Confocal line-scan imaging demonstrated Ca2+ signals elicited from individual endolysosomes (“lysosome Ca2+ sparks”) by TRPA1 activation. In physiological solutions, the TRPA1-mediated endolysosomal Ca2+ release contributed to ∼40% of the overall [Ca2+]i rise and directly triggered vesicle exocytosis and calcitonin gene-related peptide release, which greatly enhanced the excitability of DRG neurons. Thus, in addition to working via Ca2+ influx, TRPA1 channels trigger vesicle release in sensory neurons by releasing Ca2+ from lysosome-like organelles.


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