TRPC1-5-5-5 heteromer as a sodium sensor
Hana Kang1, Jinhyeong Kim1, Insuk So1
1Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Biochemical and Biophysical Research Communications
|July 5, 2025
Summary
Researchers identified how TRPC1 and TRPC5 channels combine and activate. Increased internal sodium selectively activates TRPC1/5 channels, revealing crucial molecular mechanisms for TRPC channel function.
Area of Science:
- Molecular biology
- Cell physiology
- Ion channel research
Background:
- Transient Receptor Potential Canonical (TRPC) channels are crucial for calcium (Ca²⁺) permeability in mammalian cells.
- TRPC5, a non-selective cation channel, is involved in membrane depolarization and calcium influx.
- TRPC5 forms homotetramers and heterotetramers with TRPC1, suggesting complex channel assembly and function.
Purpose of the Study:
- To investigate the subunit composition and activation mechanisms of TRPC1/5 channels.
- To confirm optimal co-expression of TRPC1-5 and TRPC5-5 concatemers.
- To elucidate the role of Gi2QL, internal calcium, and sodium in TRPC1/5 channel activity.
Main Methods:
- Optimal co-expression of TRPC1-5 and TRPC5-5 concatemers.
- Gi2QL activation experiments to assess concatemeric current.
- Manipulation of internal calcium and sodium concentrations to study channel activation.
- Structural modeling to identify potential Na⁺-binding sites.
Main Results:
- Gi2QL activation leads to ideal concatemeric current for both TRPC1-5 and TRPC5-5.
- Increased internal calcium exclusively activates the TRPC5-5 homomeric concatemer.
- Increased internal sodium selectively activates the TRPC1-5-5-5 concatemer.
- Structural modeling suggests a Na⁺-binding site at the TRPC1-5 interface.
Conclusions:
- The study clarifies the subunit composition of TRPC1/5 channels.
- Molecular mechanisms for TRPC1/5 channel activation by ions have been elucidated.
- Identified sodium sensitivity provides insights into channel gating and regulation.
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