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Murine cardiac growth, TRPC channels, and cGMP kinase I

  • Signaling and cell physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Signaling via cGMP-dependent protein kinase I (cGKI) and canonical transient receptor potential (TRPC) channels appears to be involved in the regulation of cardiac hypertrophy. Recent evidence suggests that TRPC channels are targets for cGKI, and phosphorylation of these channels may mediate the antihypertrophic effects of cGMP signaling. We tested this concept by investigating the role of cGMP/cGKI signaling on angiotensin II (A II)-induced cardiac hypertrophy using a control group (Ctr), trpc6−/−, trpc3−/−, trpc3−/−/6−/−, βRM mice, and trpc3−/−/6−/− × βRM mice. βRM mice express cGKIβ only in the smooth muscle on a cGKI−/− background. The control group was composed of littermate mice that contained at least one wild type gene of the respective genotype. A II was infused by minipumps (7 days; 2 mg/kg/day) in Ctr, trpc6−/−, trpc3−/−, trpc3−/−/6−/−, βRM, and trpc3−/−/6−/− × βRM mice. Hypertrophy was assessed by measuring heart weight per tibia length (HW/TL) and fibrosis by staining of heart slices. A II-induced increase in HW/TL and fibrosis was absent in trpc3−/− mice, whereas an increase in HW/TL and fibrosis was evident in Ctr and trpc6−/−, minimal or absent in trpc3−/−, moderate in βRM, and dramatic in trpc3−/−/6−/− βRM mice. These results suggest that TRPC3 may be necessary for A II-induced cardiac hypertrophy. On the other hand, hypertrophy and fibrosis were massively increased in βRM mice on a TRPC3/6 × cGKI−/−KO background, indicating an “additive” coupling between both signaling pathways.

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Acknowledgments

We thank Teodora Kennel for expert technical support.

Funding

The experimental work was supported by grants from Deutsche Forschungsgemeinschaft, Fond der Chemischen Industrie, and by the Intramural Research Program of the NIH (Project Z01-ES-101684 to LB).

Conflict of interest

None declared

Author information

Authors and Affiliations

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

    Katrin Domes, Enrico Patrucco, Florian Loga, Jörg W. Wegener & Franz Hofmann

  2. Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität, Munich, Germany

    Alexander Dietrich

  3. National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, 27709, USA

    Lutz Birnbaumer

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  1. Katrin Domes
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  2. Enrico Patrucco
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  3. Florian Loga
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  4. Alexander Dietrich
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Correspondence to Franz Hofmann.

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Domes, K., Patrucco, E., Loga, F. et al. Murine cardiac growth, TRPC channels, and cGMP kinase I. Pflugers Arch - Eur J Physiol 467, 2229–2234 (2015). https://doi.org/10.1007/s00424-014-1682-0

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  • DOI: https://doi.org/10.1007/s00424-014-1682-0

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