Literature DB >> 28792844

TRPA1 ion channel stimulation enhances cardiomyocyte contractile function via a CaMKII-dependent pathway.

Spencer R Andrei1, Monica Ghosh2, Pritam Sinharoy3, Souvik Dey2, Ian N Bratz4, Derek S Damron2.   

Abstract

RATIONALE: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disk, costamere and intercalated disk. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored.
OBJECTIVE: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action. METHODS AND
RESULTS: Freshly isolated CMs were obtained from murine heart and loaded with Fura-2 AM. Simultaneous measurement of intracellular free Ca2+ concentration ([Ca2+]i) and contractility was performed in individual CMs paced at 0.3 Hz. Our findings demonstrate that TRPA1 stimulation with AITC results in a dose-dependent increase in peak [Ca2+]i and a concomitant increase in CM fractional shortening. Further analysis revealed a dose-dependent acceleration in time to peak [Ca2+]i and velocity of shortening as well as an acceleration in [Ca2+]i decay and velocity of relengthening. These effects of TRPA1 stimulation were not observed in CMs pre-treated with the TRPA1 antagonist, HC-030031 (10 µmol/L) nor in CMs obtained from TRPA1-/- mice. Moreover, we observed no significant increase in cAMP levels or PKA activity in response to TRPA1 stimulation and the PKA inhibitor peptide (PKI 14-22; 100 nmol/L) failed to have any effect on the TRPA1-mediated increase in CM contractile function. However, TRPA1 stimulation resulted in a rapid phosphorylation of Ca2+/calmodulin-dependent kinase II (CaMKII) (1-5 min) that correlated with increases in CM [Ca2+]i and contractile function. Finally, all aspects of TRPA1-dependent increases in CM [Ca2+]i, contractile function and CaMKII phosphorylation were virtually abolished by the CaMKII inhibitors, KN-93 (10 µmol/L) and autocamtide-2-related peptide (AIP; 20 µmol/L).
CONCLUSIONS: These novel findings demonstrate that stimulation of TRPA1 ion channels in CMs results in activation of a CaMKII-dependent signaling pathway resulting in modulation of intracellular Ca2+ availability and handling leading to increases in CM contractile function. Cardiac TRPA1 ion channels may represent a novel therapeutic target for increasing the inotropic and lusitropic state of the heart.

Entities:  

Keywords:  CaMKII; TRPA1; [Ca2+]i; cardiomyocytes; contractility

Mesh:

Substances:

Year:  2017        PMID: 28792844      PMCID: PMC5786180          DOI: 10.1080/19336950.2017.1365206

Source DB:  PubMed          Journal:  Channels (Austin)        ISSN: 1933-6950            Impact factor:   2.581


  34 in total

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Authors:  Jack Rubinstein; Valerie M Lasko; Sheryl E Koch; Vivek P Singh; Vinicius Carreira; Nathan Robbins; Amit R Patel; Min Jiang; Philip Bidwell; Evangelia G Kranias; W Keith Jones; John N Lorenz
Journal:  Am J Physiol Heart Circ Physiol       Date:  2013-12-06       Impact factor: 4.733

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Journal:  J Biol Chem       Date:  1997-02-21       Impact factor: 5.157

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Journal:  J Biol Chem       Date:  1981-10-25       Impact factor: 5.157

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Journal:  J Mol Cell Cardiol       Date:  1983-09       Impact factor: 5.000

Review 7.  Regulation of cardiac contractile function by troponin I phosphorylation.

Authors:  Joanne Layland; R John Solaro; Ajay M Shah
Journal:  Cardiovasc Res       Date:  2005-04-01       Impact factor: 10.787

8.  Phosphorylation of phospholamban and troponin I in beta-adrenergic-induced acceleration of cardiac relaxation.

Authors:  L Li; J Desantiago; G Chu; E G Kranias; D M Bers
Journal:  Am J Physiol Heart Circ Physiol       Date:  2000-03       Impact factor: 4.733

Review 9.  Role of phospholamban phosphorylation on Thr17 in cardiac physiological and pathological conditions.

Authors:  Alicia Mattiazzi; Cecilia Mundiña-Weilenmann; Chu Guoxiang; Leticia Vittone; Evangelia Kranias
Journal:  Cardiovasc Res       Date:  2005-10-13       Impact factor: 10.787

10.  Propofol attenuates beta-adrenoreceptor-mediated signal transduction via a protein kinase C-dependent pathway in cardiomyocytes.

Authors:  Hiromi Kurokawa; Paul A Murray; Derek S Damron
Journal:  Anesthesiology       Date:  2002-03       Impact factor: 7.892

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  14 in total

1.  TRPV4 deletion protects heart from myocardial infarction-induced adverse remodeling via modulation of cardiac fibroblast differentiation.

Authors:  Ravi K Adapala; Anantha K Kanugula; Sailaja Paruchuri; William M Chilian; Charles K Thodeti
Journal:  Basic Res Cardiol       Date:  2020-01-10       Impact factor: 17.165

2.  TRPA1 channel contributes to myocardial ischemia-reperfusion injury.

Authors:  Daniel J Conklin; Yiru Guo; Matthew A Nystoriak; Ganapathy Jagatheesan; Detlef Obal; Peter J Kilfoil; Joseph David Hoetker; Luping Guo; Roberto Bolli; Aruni Bhatnagar
Journal:  Am J Physiol Heart Circ Physiol       Date:  2019-02-08       Impact factor: 4.733

3.  Mouse embryonic stem cell-derived cardiomyocytes cease to beat following exposure to monochromatic light: association with increased ROS and loss of calcium transients.

Authors:  Gurbind Singh; Divya Sridharan; Mahmood Khan; Polani B Seshagiri
Journal:  Am J Physiol Cell Physiol       Date:  2019-07-17       Impact factor: 4.249

4.  Transient receptor potential ankyrin 1 (trpa1) mediates il-1β-induced apoptosis in rat chondrocytes via calcium overload and mitochondrial dysfunction.

Authors:  Songjiang Yin; Li Zhang; Liang Ding; Zhengquan Huang; Bo Xu; XiaoChen Li; Peimin Wang; Jun Mao
Journal:  J Inflamm (Lond)       Date:  2018-12-17       Impact factor: 4.981

5.  Stimulation of TRPA1 attenuates ischemia-induced cardiomyocyte cell death through an eNOS-mediated mechanism.

Authors:  Spencer R Andrei; Monica Ghosh; Pritam Sinharoy; Derek S Damron
Journal:  Channels (Austin)       Date:  2019-12       Impact factor: 2.581

Review 6.  The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges.

Authors:  Zhen Wang; Di Ye; Jing Ye; Menglong Wang; Jianfang Liu; Huimin Jiang; Yao Xu; Jishou Zhang; Jiangbin Chen; Jun Wan
Journal:  Front Pharmacol       Date:  2019-10-18       Impact factor: 5.810

Review 7.  Transient receptor potential channels in cardiac health and disease.

Authors:  Thomas Hof; Sébastien Chaigne; Alice Récalde; Laurent Sallé; Fabien Brette; Romain Guinamard
Journal:  Nat Rev Cardiol       Date:  2019-06       Impact factor: 32.419

Review 8.  Targeting Ca2 + Handling Proteins for the Treatment of Heart Failure and Arrhythmias.

Authors:  Alexandra Njegic; Claire Wilson; Elizabeth J Cartwright
Journal:  Front Physiol       Date:  2020-09-04       Impact factor: 4.566

9.  TRPA1 Activation-Induced Myelin Degradation Plays a Key Role in Motor Dysfunction After Intracerebral Hemorrhage.

Authors:  Min Xia; Weixiang Chen; Jie Wang; Yi Yin; Chao Guo; Chengcheng Li; Mingxi Li; Xiaoqin Tang; Zhengcai Jia; Rong Hu; Xin Liu; Hua Feng
Journal:  Front Mol Neurosci       Date:  2019-04-17       Impact factor: 5.639

Review 10.  Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases.

Authors:  Jianlin Feng; Maria K Armillei; Albert S Yu; Bruce T Liang; Loren W Runnels; Lixia Yue
Journal:  J Cardiovasc Dev Dis       Date:  2019-09-23
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