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Updated: Apr 19, 2026

In vitro Assessment of Cardiac Reprogramming by Measuring Cardiac Specific Calcium Flux with a GCaMP3 Reporter
05:04

In vitro Assessment of Cardiac Reprogramming by Measuring Cardiac Specific Calcium Flux with a GCaMP3 Reporter

Published on: February 22, 2022

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Murine cardiac growth, TRPC channels, and cGMP kinase I

Katrin Domes1, Enrico Patrucco1, Florian Loga1

  • 1FOR923, Institut für Pharmakologie und Toxikologie, Technische Universität München, Biedersteiner Str. 29, 80802, Munich, Germany.

Pflugers Archiv : European Journal of Physiology
|December 31, 2014
PubMed

Insights

Transient Receptor Potential Canonical 3 (TRPC3) channels are essential for angiotensin II-induced cardiac hypertrophy. Disrupting TRPC3 prevents hypertrophy, while combined TRPC3/6 and cGMP-dependent protein kinase I (cGKI) disruption exacerbates it.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Ion Channel Physiology

Background:

  • Cardiac hypertrophy is regulated by cGMP-dependent protein kinase I (cGKI) and canonical transient receptor potential (TRPC) channels.
  • TRPC channels are potential targets of cGKI, with phosphorylation mediating cGMP's antihypertrophic effects.

Purpose of the Study:

  • To investigate the role of cGMP/cGKI signaling in angiotensin II (A II)-induced cardiac hypertrophy.
  • To determine if TRPC3 and TRPC6 channels mediate the effects of cGMP signaling on cardiac hypertrophy.

Main Methods:

  • Utilized various genetically modified mouse models: wild-type controls, trpc6(-/-), trpc3(-/-), trpc3(-/-)/6(-/-), $\beta$RM mice (smooth muscle-specific cGKI$\\beta$ expression), and trpc3(-/-)/6(-/-) x $\beta$RM mice.
  • Administered angiotensin II (A II) via minipumps for 7 days.
  • Assessed cardiac hypertrophy by heart weight to tibia length ratio (HW/TL) and cardiac fibrosis via heart slice staining.

Main Results:

  • A II-induced cardiac hypertrophy and fibrosis were absent in trpc3(-/-) mice.
  • Significant increases in HW/TL and fibrosis were observed in control and trpc6(-/-) mice.
  • Hypertrophy was minimal in trpc3(-/-) mice, moderate in $\beta$RM mice, and dramatically increased in trpc3(-/-)/6(-/-) x $\beta$RM mice.
  • An additive interaction between TRPC3/6 and cGKI pathways was indicated by massive hypertrophy in double knockout mice.

Conclusions:

  • TRPC3 channels are necessary for angiotensin II-induced cardiac hypertrophy.
  • The interplay between TRPC channels and cGKI signaling is crucial in regulating cardiac hypertrophy, with TRPC3 playing a key role.
Keywords:
Cardiac myocytesEndothelium/fibrocytesNitric oxide/PKG-ISignal transductionTRPC channels

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