Related Experiment Video

Updated: Aug 19, 2025

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
08:27

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

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TRPC channels blockade abolishes endotoxemic cardiac dysfunction by hampering intracellular inflammation and Ca2+

Na Tang1,2, Wen Tian3,4, Guang-Yuan Ma1,2

  • 1Department of Pharmacy, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, China.

Nature Communications
|December 2, 2022
PubMed

Insights

Targeting TRPC1 and TRPC6 channels, crucial for calcium regulation, can treat septic cardiac dysfunction. Blocking these channels prevents calcium leaks and inflammation, improving heart function and survival in sepsis models.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Immunology

Background:

  • Sepsis-induced cardiac dysfunction involves intracellular calcium dysregulation.
  • Conventional calcium regulatory pathways do not fully resolve this condition.

Purpose of the Study:

  • To investigate the role of Transient Receptor Potential Canonical (TRPC) channels TRPC1 and TRPC6 in septic cardiac dysfunction.
  • To explore TRPC1/TRPC6 as therapeutic targets for sepsis-related heart failure.

Main Methods:

  • Utilized knockout mouse models for Trpc1 and Trpc6.
  • Assessed lipopolysaccharide (LPS)-induced cardiac dysfunction and survival rates.
  • Investigated calcium (Ca2+) release from the endoplasmic reticulum in cardiomyocytes and macrophages.
  • Examined the interaction between calmodulin, TRPC channels, and Toll-like receptor 4 (TLR4).
  • Tested a chemical inhibitor targeting the TRPC C-terminal CaM/IP3R binding domain.

Main Results:

  • Trpc1 or Trpc6 knockout significantly ameliorated LPS-induced heart failure and prolonged survival in mice.
  • Knockout of Trpc1 or Trpc6 inhibited LPS-triggered Ca2+ release from the endoplasmic reticulum.
  • Calmodulin uncoupling from TRPC channels in Trpc1/Trpc6 deficient cells blocked the TLR4-mediated inflammation cascade.
  • Chemical inhibition of the TRPC C-terminal CaM/IP3R binding domain demonstrated cardioprotective effects.

Conclusions:

  • TRPC1 and TRPC6 channels are critical mediators of calcium dysregulation and inflammation in septic cardiac dysfunction.
  • Targeting TRPC1/TRPC6 channels offers a novel therapeutic strategy for endotoxemia and sepsis-related heart failure.

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