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TRPC Channels in Cardiac Hypertrophy

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Pathologies of Calcium Channels

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Abstract

Impaired cardiomyocyte Ca2+ handling is considered as crucial factor programming cardiac hypertrophy and heart failure. It has, however, not been entirely resolved what type of Ca2+ signals is involved in mechanisms inducing hypertrophic remodelling. Ca2+ microdomains, which are restricted from the fluctuating Ca2+ during excitation–contraction coupling, could generate local Ca2+ signals and activate downstream Ca2+ dependent signalling pathways. With the non-selective ion channels of the TRPC family, attractive entities in microdomain Ca2+ signalling have been found. Within a short period of time important aspects of TRPC dependent signalling have been revealed. TRPC channels contribute to a store-operated Ca2+ entry, are functionally cross-linked with L-type Ca2+ channels and can indirectly sense stress stimuli during cardiac hypertrophy. Pressure-overload or agonist stimulation of the heart results in an increased TRPC channel activity which is mechanistically coupled to Ca2+ dependent signalling pathways. In particular, the calcineurin/nuclear factor of activated T-cells signalling pathway has been elucidated as central mediator translating TRPC dependent Ca2+ signals to hypertrophic cardiac growth. Interference with the TRPC/calcineurin/nuclear factor of activated T-cells circuit or TRPC blockade has been found beneficial in opposing cardiac remodelling. TRPC channels can therefore be regarded as promising targets in the therapy of heart failure

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Authors and Affiliations

  1. Department of Internal Medicine I—Cardiology, University Hospital Würzburg, Würzburg, Germany

    Nadine Kirschmer & Petra Eder-Negrin

  2. Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany

    Nadine Kirschmer & Petra Eder-Negrin

  3. Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany

    Kristina Lorenz

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  1. Nadine Kirschmer
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  2. Kristina Lorenz
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  3. Petra Eder-Negrin
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Correspondence to Petra Eder-Negrin .

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Editors and Affiliations

  1. Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada

    Norbert Weiss

  2. Department of Neurophysiology and Pharmacology, Medical University Vienna, Vienna, Austria

    Alexandra Koschak

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Kirschmer, N., Lorenz, K., Eder-Negrin, P. (2014). TRPC Channels in Cardiac Hypertrophy . In: Weiss, N., Koschak, A. (eds) Pathologies of Calcium Channels. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40282-1_22

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