Cellular context determines primary characteristics of human TRPC5 as a cold-activated channel
Alexandra Ptakova1,2, Michal Mitro1,2, Lucie Zimova1
1Department of Cellular Neurophysiology, Institute of Physiology Czech Academy of Sciences, Prague, Czech Republic.
Journal of Cellular Physiology
|June 28, 2022
Summary
Human TRPC5 channels are intrinsically cold-sensitive, playing a role in pain perception. Their cold gating depends on protein phosphorylation and calcium levels, revealing insights into pain signaling.
Area of Science:
- Neuroscience
- Ion Channel Physiology
- Pain Research
Background:
- The human transient receptor potential canonical 5 (TRPC5) channel is crucial for various pain types, including cold pain.
- TRPC5's cold sensitivity is known, but whether this is an intrinsic property or influenced by the cellular environment remains unclear.
Purpose of the Study:
- To investigate the intrinsic cold sensitivity of the human TRPC5 channel at the single-channel level.
- To determine the influence of cellular environment and specific mutations on TRPC5's cold-gated properties.
Main Methods:
- Utilized single-channel electrophysiology in transiently transfected HEK293T cells to study human TRPC5.
- Analyzed changes in open dwell times, open probability (Po), and unitary current amplitude with varying temperatures.
- Investigated mutant TRPC5 channels (T970A and a mutant disrupting STIM1 interaction) to assess environmental influences.
Main Results:
- Decreasing temperature significantly increased TRPC5 open probability and mean open dwell times, while reducing current amplitude.
- TRPC5 exhibited intrinsic cold gating with a steep response between 16°C-11°C, saturating below 8-5°C.
- Mutations affecting G-protein coupled receptor signaling or STIM1 interaction altered TRPC5's cold sensitivity and activation threshold.
Conclusions:
- Human TRPC5 functions as an intrinsically cold-gated ion channel.
- TRPC5's cold sensitivity is modulated by protein phosphorylation and intracellular calcium homeostasis.
- These findings provide a deeper understanding of TRPC5's role in cold pain signaling.
Keywords:
HEK293TTRPC cation channelscold temperaturesingle channelsstromal interaction molecule 1thermosensitive TRPMore Related Videos
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