• Nanion技术: 离子通道研究的智能工具

    Nanion技术: 离子通道研究的智能工具

  • CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

    CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

  • SURFE²R 96SE: 非标记高通量转运体筛选

    SURFE²R 96SE: 非标记高通量转运体筛选

  • 脂双层记录: Orbit产品系列

    脂双层记录: Orbit产品系列

我们的产品目录

SyncroPatch 384i

SyncroPatch 384i

Patchliner

Patchliner

Port-a-Patch

Port-a-Patch

Port-a-Patch mini

Port-a-Patch mini

CardioExcyte 96

CardioExcyte 96

FLEXcyte 96

FLEXcyte 96

SURFE²R 96SE

SURFE²R 96SE

SURFE²R N1

SURFE²R N1

Orbit 16

Orbit 16

Orbit Mini

Orbit Mini

Vesicle Prep Pro

Vesicle Prep Pro

2014 - Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain

icon pap  Port-a-Patch and   icon vpp   Vesicle Prep Pro publication in Proceedings of the National Academy of Sciences of the United States of America (2014)

Authors: 
Moparthi L., Survery S., Kreir M., Simonsen C., Kjellbom P., Högestätt E.D., Johanson U., Zygmunt P.M.

Journal: 
Proc Natl Acad Sci U S A. (2014) 111(47):16901-6.


Abstract: 

We have purified and reconstituted human transient receptor potential (TRP) subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to understand its inherent thermo- and chemosensory properties as well as the role of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We report that hTRPA1 with and without its N-terminal ARD (Δ1–688 hTRPA1) is intrinsically cold-sensitive, and thus, cold-sensing properties of hTRPA1 reside outside the N-terminal ARD. We show activation of hTRPA1 by the thiol oxidant 2-((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin) and that electrophilic compounds activate hTRPA1 in the presence and absence of the N-terminal ARD. The nonelectrophilic compounds menthol and the cannabinoid Δ9-tetrahydrocannabiorcol (C16) directly activate hTRPA1 at different sites independent of the N-terminal ARD. The TRPA1 antagonist HC030031 inhibited cold and chemical activation of hTRPA1 and Δ1–688 hTRPA1, supporting a direct interaction with hTRPA1 outside the N-terminal ARD. These findings show that hTRPA1 is an intrinsically cold- and chemosensitive ion channel. Thus, second messengers, including Ca2+, or accessory proteins are not needed for hTRPA1 responses to cold or chemical activators. We suggest that conformational changes outside the N-terminal ARD by cold, electrophiles, and nonelectrophiles are important in hTRPA1 channel gating and that targeting chemical interaction sites outside the N-terminal ARD provides possibilities to fine tune TRPA1-based drug therapies (e.g., for treatment of pain associated with cold hypersensitivity and cardiovascular disease).


Download here

返回总览

Nanion运营博客

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies).

You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.