Cellular context determines primary characteristics of human TRPC5 as a cold-activated channel

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F22%3A00561637" target="_blank" >RIV/67985823:_____/22:00561637 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/22:10452947

Result on the web

<a href="https://doi.org/10.1002/jcp.30821" target="_blank" >https://doi.org/10.1002/jcp.30821</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/jcp.30821" target="_blank" >10.1002/jcp.30821</a>

Result language

angličtina

Original language name

Cellular context determines primary characteristics of human TRPC5 as a cold-activated channel

Original language description

The human transient receptor potential canonical 5 (TRPC5) is a calcium-permeable, nonselective cation channel expressed in the central and peripheral nervous system and also in other tissues such as the kidney, synovium, and odontoblasts. TRPC5 has been recently confirmed to play a key role in spontaneous, inflammatory mechanical, and cold pain. Although TRPC5 activation is known to be cold sensitive, it is unclear whether this property is intrinsic to the channel protein and whether or to what extent it may be determined by the cellular environment. In this study, we explored the cold sensitivity of human TRPC5 at the single-channel level using transiently transfected HEK293T cells. Upon decreasing the temperature, the channel demonstrated prolonged mean open dwell times and a robust increase in the open probability (P-o), whereas the amplitude of unitary currents decreased similar to 1.5-fold per 10 degrees C of temperature difference. In the absence of any agonists, the temperature dependence of P-o was sigmoidal, with a steep slope within the temperature range of 16 degrees C-11 degrees C, and exhibited saturation below 8-5 degrees C. Thermodynamic analysis revealed significant changes in enthalpy and entropy, suggesting that substantial conformational changes accompany cold-induced gating. The mutant channel T970A, in which the regulation downstream of G-protein coupled receptor signaling was abrogated, exhibited higher basal activity at room temperature and a less steep temperature response profile, with an apparent threshold below 22 degrees C. An even more pronounced decrease in the activation threshold was observed in a mutant that disrupted the electrostatic interaction of TRPC5 with the endoplasmic reticulum calcium sensor stromal interaction molecule 1. Thus, TRPC5 exhibits features of an intrinsically cold-gated channel, its sensitivity to cold tightly depends on the phosphorylation status of the protein and intracellular calcium homeostasis.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/GA22-13750S" target="_blank" >GA22-13750S: Signaling pathways affecting human TRPC5 receptor function: Prediction of their association with rheumatoid arthritis pain</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Cellular Physiology

ISSN

0021-9541

e-ISSN

1097-4652

Volume of the periodical

237

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

3614-3626

UT code for WoS article

000816966300001

EID of the result in the Scopus database

2-s2.0-85132880697