Metabolic Inhibition Induces Transient Increase of L-type Ca2+ Current in Human and Rat Cardiac Myocytes - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue International Journal of Molecular Sciences Année : 2019

Metabolic Inhibition Induces Transient Increase of L-type Ca2+ Current in Human and Rat Cardiac Myocytes

Résumé

Metabolic inhibition is a common condition observed during ischemic heart disease and heart failure. It is usually accompanied by a reduction in L-type Ca 2+ channel (LTCC) activity. In this study, however, we show that metabolic inhibition results in a biphasic effect on LTCC current (ICaL) in human and rat cardiac myocytes: an initial increase of ICaL is observed in the early phase of metabolic inhibition, which is followed by the more classical and strong inhibition. We studied the mechanism of the initial increase of ICaL in cardiac myocytes during a non-selective β-adrenergic stimulation with isoprenaline. The initial increase of ICaL was induced by a wide range of metabolic inhibitors (FCCP, 2,4-DNP, rotenone, antimycin A). In rat cardiomyocytes, the initial increase of ICaL was eliminated when the cells were pre-treated with thapsigargin leading to the depletion of Ca 2+ from the sarcoplasmic reticulum (SR). Similar results were obtained when Ca 2+ release from the SR was blocked with ryanodine. These data suggest that the increase of ICaL in the early phase of metabolic inhibition is due to a reduced calcium dependent inactivation (CDI) of LTCCs. This was further confirmed in human atrial myocytes where FCCP failed to induce the initial stimulation of ICaL when Ca 2+ was replaced by Ba 2+ eliminating CDI of LTCCs. We conclude that the initial increase in ICaL observed during metabolic inhibition in human and rat cardiomyocytes is a consequence of an acute reduction of Ca 2+ release from SR resulting in reduced CDI of LTCCs.
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Dates et versions

hal-02463699 , version 1 (01-02-2020)
hal-02463699 , version 2 (24-02-2020)

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Rimantas Treinys, Giedrius Kanaporis, Rodolphe Fischmeister, Jonas Jurevičius. Metabolic Inhibition Induces Transient Increase of L-type Ca2+ Current in Human and Rat Cardiac Myocytes. International Journal of Molecular Sciences, 2019, 20 (6), pp.1501. ⟨10.3390/ijms20061501⟩. ⟨hal-02463699v1⟩
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