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TRPC3 as a key player in electrical remodelling of atrial myocardium

Recent evidence suggests involvement of transient receptor potential (TRP)-related cation channels in cardiac physiology and pathophysiology, with TRPC3 as one potential key player in cardiac hypertrophy. It has been suggested that TRPC3 is upregulated in hypertrophy development and contributes to Ca2+ signals that govern pathological remodelling. As TRPC proteins form nonselective cation channels, we hypothesized that these molecules determine not only Ca2+-mediated gene expression but also excitability and basic electrical properties of the myocardium in pathological states. We utilized the patch clamp technique to characterize the electrical remodelling associated with enhanced TRPC3 expression in cardiac myocytes. The murine HL-1 atrial cell model, which was found to express both TRPC3 and TRPC6 at low levels along with typical signalling partners of TRPC proteins such as Na+/Ca2+-exchanger-1 and CaV1.2, was modified to overexpress a functional YFP-TRPC3 fusion protein. TRPC3 over-expressing cells displayed substantially altered electrical properties even in the absence of TRPC-activating stimuli, as evident from a significant shortening of basal action potential duration and impaired frequency-dependent adaptation of action potential shape. Action potential-clamp experiments as well as mathematical modelling attempts were performed to delineate the consequences of TRPC3 overexpression and to analyze the mechanisms of TRPC3-mediated electrical remodelling in the heart. Our results suggest a pivotal role of TRPC channels in cardiac electrical remodelling associated with maladaptive hypertrophy.

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Correspondence to Klaus Groschner.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Saad, Z., Eder, P., Zorn-Pauly, K. et al. TRPC3 as a key player in electrical remodelling of atrial myocardium. BMC Pharmacol 8 (Suppl 1), A31 (2008).

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  • Transient Receptor Potential
  • Action Potential Duration
  • Nonselective Cation Channel
  • TRPC Channel
  • Electrical Remodelling