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Proc Natl Acad Sci U S A. 2019 Mar 12;116(11):5170-5175. doi: 10.1073/pnas.1819635116. Epub 2019 Feb 25.

Recovery from tachyphylaxis of TRPV1 coincides with recycling to the surface membrane.

Author information

1
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072 Hubei, China.
2
Sorbonne Université, Institut de Biologie de Paris-Seine, Neuroscience Paris Seine, CNRS UMR8246, INSERM U1130, 75005 Paris, France.
3
Sorbonne Université, Institut de Biologie de Paris-Seine, Neuroscience Paris Seine, CNRS UMR8246, INSERM U1130, 75005 Paris, France dongdong.li@inserm.fr jyao@whu.edu.cn.
4
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072 Hubei, China; dongdong.li@inserm.fr jyao@whu.edu.cn.

Abstract

The transient receptor potential vanilloid-1 (TRPV1) ion channel is essential for sensation of thermal and chemical pain. TRPV1 activation is accompanied by Ca2+-dependent desensitization; acute desensitization reflects rapid reduction in channel activity during stimulation, whereas tachyphylaxis denotes the diminution in TRPV1 responses to repetitive stimulation. Acute desensitization has been attributed to conformational changes of the TRPV1 channel; however, the mechanisms underlying the establishment of tachyphylaxis remain to be defined. Here, we report that the degree of whole-cell TRPV1 tachyphylaxis is regulated by the strength of inducing stimulation. Using light-sheet microscopy and pH-sensitive sensor pHluorin to follow TRPV1 endocytosis and exocytosis trafficking, we provide real-time information that tachyphylaxis of different degrees concurs with TRPV1 recycling to the plasma membrane in a proportional manner. This process controls TRPV1 surface expression level thereby the whole-cell nociceptive response. We further show that activity-gated TRPV1 trafficking associates with intracellular Ca2+ signals of distinct kinetics, and recruits recycling routes mediated by synaptotagmin 1 and 7, respectively. These results suggest that activity-dependent TRPV1 recycling contributes to the establishment of tachyphylaxis.

KEYWORDS:

TRP channel; calcium; desensitization; pain; synaptotagmin

PMID:
30804201
PMCID:
PMC6421460
[Available on 2019-08-25]
DOI:
10.1073/pnas.1819635116
[Indexed for MEDLINE]

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