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


ABSTRACT: Metabolic inhibition is a common condition observed during ischemic heart disease and heart failure. It is usually accompanied by a reduction in L-type Ca2+ 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 ?-adrenergic stimulation by isoprenaline, a non-selective agonist of ?-adrenergic receptors. The whole-cell patch?clamp technique was used to record the ICaL in single cardiac myocytes. 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 Ca2+ from the sarcoplasmic reticulum (SR). Similar results were obtained when Ca2+ 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 Ca2+ was replaced by Ba2+, eliminating CDI of LTCCs. We conclude that the initial increase in ICaL observed during the metabolic inhibition in human and rat cardiomyocytes is a consequence of an acute reduction of Ca2+ release from SR resulting in reduced CDI of LTCCs.

SUBMITTER: Treinys R 

PROVIDER: S-EPMC6471217 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Metabolic Inhibition Induces Transient Increase of L-type Ca<sup>2+</sup> Current in Human and Rat Cardiac Myocytes.

Treinys Rimantas R   Kanaporis Giedrius G   Fischmeister Rodolphe R   Jurevičius Jonas J  

International journal of molecular sciences 20190326 6


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<sup>2+</sup> channel (LTCC) activity. In this study, however, we show that metabolic inhibition results in a biphasic effect on LTCC current (I<sub>CaL</sub>) in human and rat cardiac myocytes: an initial increase of I<sub>CaL</sub> is observed in the early phase of metabolic inhibition which is followed by the more classical and strong inhibi  ...[more]

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