Dataset Information

TRPC4? and TRPC4? Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.

ABSTRACT: The Transient Receptor Potential Channel Subunit 4 (TRPC4) has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. G?q protein-coupled receptor (GPCR) stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT) activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4? and TRPC4?. Aim of the present study was to analyze cytosolic Ca2+ signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4? or TRPC4?. The analysis of Ca2+ transients in neonatal rat cardiomyocytes (NRCs) showed that TRPC4? and TRPC4? affected Ca2+ cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca2+ transient amplitude at baseline and TRPC4? increasing the Ca2+ peak during angiotensin II (Ang II) stimulation. NRCs infected with TRPC4? (Ad-C4?) also responded with a sustained Ca2+ influx when treated with Ang II under non-pacing conditions. Consistent with the Ca2+ data, NRCs infected with TRPC4? (Ad-C4?) showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4? reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4? NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not translated into an increased propensity towards hypertrophy but rather less hypertrophy during GPCR stimulation. Further analyses revealed that, although hypertrophy was preserved in Ad-C4? NRCs and even attenuated in Ad-C4? NRCs, cardiomyocytes had an increased apoptosis rate and thus were less viable after chronic GPCR stimulation. These findings suggest that TRPC4? and TRPC4? differentially affect Ca2+ signals, calcineurin/NFAT signaling and hypertrophy but similarly impair cardiomyocyte viability during GPCR stimulation.

SUBMITTER: Kirschmer N

PROVIDER: S-EPMC5167390 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.

Kirschmer Nadine N Bandleon Sandra S von Ehrlich-Treuenstätt Viktor V Hartmann Sonja S Schaaf Alice A Lamprecht Anna-Karina AK Miranda-Laferte Erick E Langsenlehner Tanja T Ritter Oliver O Eder Petra P

PloS one 20161219 12

The Transient Receptor Potential Channel Subunit 4 (TRPC4) has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR) stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ s ...[more]

PMID: 27992507

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Dataset Information

TRPC4? and TRPC4? Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.

Publications

TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation.

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