Two-pore channels (TPCs) acts as a hub for excitation-contraction coupling, metabolism and cardiac hypertrophy signalling.

Autor: de Zélicourt A; Université Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France; Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, CNRS- Université Paris-Saclay, Saclay, 91400, France., Fayssoil A; Université Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France., Mansart A; Université Paris-Saclay, UVSQ, Inserm, 2I, 78000 Versailles, France., Zarrouki F; Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, CNRS- Université Paris-Saclay, Saclay, 91400, France., Karoui A; UMR-S 1180, INSERM, Signaling and cardiovascular pathophysiology, Université Paris-Saclay, 91400 Orsay, France., Piquereau J; UMR-S 1180, INSERM, Signaling and cardiovascular pathophysiology, Université Paris-Saclay, 91400 Orsay, France., Lefebvre F; UMR-S 1180, INSERM, Signaling and cardiovascular pathophysiology, Université Paris-Saclay, 91400 Orsay, France., Gerbaud P; UMR-S 1180, INSERM, Signaling and cardiovascular pathophysiology, Université Paris-Saclay, 91400 Orsay, France., Mika D; UMR-S 1180, INSERM, Signaling and cardiovascular pathophysiology, Université Paris-Saclay, 91400 Orsay, France., Dakouane-Giudicelli M; Université Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France., Lanchec E; Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, CNRS- Université Paris-Saclay, Saclay, 91400, France., Feng M; UMR-S 1176, Université Paris-Saclay, Le Kremlin Bicêtre, France., Leblais V; UMR-S 1180, INSERM, Signaling and cardiovascular pathophysiology, Université Paris-Saclay, 91400 Orsay, France., Bobe R; UMR-S 1176, Université Paris-Saclay, Le Kremlin Bicêtre, France., Launay JM; Service de Biochimie, INSERM UMR S942, Hôpital Lariboisière, Paris, France., Galione A; Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom., Gomez AM; UMR-S 1180, INSERM, Signaling and cardiovascular pathophysiology, Université Paris-Saclay, 91400 Orsay, France., de la Porte S; Université Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000 Versailles, France., Cancela JM; Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, CNRS- Université Paris-Saclay, Saclay, 91400, France. Electronic address: jose-manuel.cancela@universite-paris-saclay.fr.
Jazyk: angličtina
Zdroj: Cell calcium [Cell Calcium] 2024 Jan; Vol. 117, pp. 102839. Date of Electronic Publication: 2023 Dec 16.
DOI: 10.1016/j.ceca.2023.102839
Abstrakt: Ca 2+ signaling is essential for cardiac contractility and excitability in heart function and remodeling. Intriguingly, little is known about the role of a new family of ion channels, the endo-lysosomal non-selective cation "two-pore channel" (TPCs) in heart function. Here we have used double TPC knock-out mice for the 1 and 2 isoforms of TPCs (Tpcn1/2 -/- ) and evaluated their cardiac function. Doppler-echocardiography unveils altered left ventricular (LV) systolic function associated with a LV relaxation impairment. In cardiomyocytes isolated from Tpcn1/2 -/- mice, we observed a reduction in the contractile function with a decrease in the sarcoplasmic reticulum Ca 2+ content and a reduced expression of various key proteins regulating Ca 2+ stores, such as calsequestrin. We also found that two main regulators of the energy metabolism, AMP-activated protein kinase and mTOR, were down regulated. We found an increase in the expression of TPC1 and TPC2 in a model of transverse aortic constriction (TAC) mice and in chronically isoproterenol infused WT mice. In this last model, adaptive cardiac hypertrophy was reduced by Tpcn1/2 deletion. Here, we propose a central role for TPCs and lysosomes that could act as a hub integrating information from the excitation-contraction coupling mechanisms, cellular energy metabolism and hypertrophy signaling.
Competing Interests: Declaration of Competing Interest None.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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