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

0561637 - FGÚ 2023 RIV US eng J - Článek v odborném periodiku
Ptáková, Alexandra - Mitro, Michal - Zímová, Lucie - Vlachová, Viktorie
Cellular context determines primary characteristics of human TRPC5 as a cold-activated channel.
Journal of Cellular Physiology. Roč. 237, č. 9 (2022), s. 3614-3626. ISSN 0021-9541. E-ISSN 1097-4652
Grant CEP: GA ČR(CZ) GA22-13750S
Institucionální podpora: RVO:67985823
Klíčová slova: cold temperature * HEK293T * single channels * stromal interaction molecule 1 * thermosensitive TRP * TRPC cation channels
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 5.6, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1002/jcp.30821

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.
Trvalý link: https://hdl.handle.net/11104/0334199