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Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons.

ABSTRACT: 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.

SUBMITTER: Shang S

PROVIDER: S-EPMC5100290 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons.

Shang Shujiang S Zhu Feipeng F Liu Bin B Chai Zuying Z Wu Qihui Q Hu Meiqin M Wang Yuan Y Huang Rong R Zhang Xiaoyu X Wu Xi X Sun Lei L Wang Yeshi Y Wang Li L Xu Huadong H Teng Sasa S Liu Bing B Zheng Lianghong L Zhang Chen C Zhang Fukang F Feng Xinghua X Zhu Desheng D Wang Changhe C Liu Tao T Zhu Michael X MX Zhou Zhuan Z

The Journal of cell biology 20161031 3

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 chann ...[more]

PMID: 27799370

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Project description:BackgroundDorsal root ganglia (DRG) somata from rodents have provided an excellent model system to study ion channel properties and modulation using electrophysiological investigation. As in other vertebrates, zebrafish (Danio rerio) DRG are organized segmentally and possess peripheral axons that bifurcate into each body segment. However, the electrical properties of zebrafish DRG sensory neurons, as compared with their mammalian counterparts, are relatively unexplored because a preparation suitable for electrophysiological studies has not been available.Methodology/principal findingsWe show enzymatically dissociated DRG neurons from juvenile zebrafish expressing Isl2b-promoter driven EGFP were easily identified with fluorescence microscopy and amenable to conventional whole-cell patch-clamp studies. Two kinetically distinct TTX-sensitive Na(+) currents (rapidly- and slowly-inactivating) were discovered. Rapidly-inactivating I(Na) were preferentially expressed in relatively large neurons, while slowly-inactivating I(Na) was more prevalent in smaller DRG neurons. RT-PCR analysis suggests zscn1aa/ab, zscn8aa/ab, zscn4ab and zscn5Laa are possible candidates for these I(Na) components. Voltage-gated Ca(2+) currents (I(Ca)) were primarily (87%) comprised of a high-voltage activated component arising from ω-conotoxin GVIA-sensitive Ca(V)2.2 (N-type) Ca(2+) channels. A few DRG neurons (8%) displayed a miniscule low-voltage-activated component. I(Ca) in zebrafish DRG neurons were modulated by neurotransmitters via either voltage-dependent or -independent G-protein signaling pathway with large cell-to-cell response variability.Conclusions/significanceOur present results indicate that, as in higher vertebrates, zebrafish DRG neurons are heterogeneous being composed of functionally distinct subpopulations that may correlate with different sensory modalities. These findings provide the first comparison of zebrafish and rodent DRG neuron electrical properties and thus provide a basis for future studies.

Dataset Information

Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons.

Publications

Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons.

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