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Nguemo, Filomain, Semmler, Judith, Reppel, Michael and Hescheler, Juergen (2014). Modulation of L-type Calcium Current by Intracellular Magnesium in Differentiating Cardiomyocytes Derived from Induced Pluripotent Stem Cells. Stem Cells Dev., 23 (12). S. 1316 - 1328. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-8534

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Abstract

Intracellular Mg2+, which is implicated in arrhythmogenesis and transient cardiac ischemia, inhibits L-type Ca2+ calcium channel current (I-CaL) of adult cardiomyocytes (CMs). We take the advantage of an in vitro model of CMs based on induced pluripotent stem cells to investigate the effects of intracellular Mg2+ on the phosphorylation or dephosphorylation processes of L-type Ca2+ channels (LTCCs) at early and late stages of cardiac cell differentiation. Using the whole-cell patch-clamp technique, we demonstrate that increasing intracellular Mg2+ concentration [Mg2+](i) from 0.2 to 5mM markedly reduced the peak of I-CaL density, showing less effect on both the activation and inactivation properties in the late differentiation stage (LDS) of CMs more so than in the early differentiation stage (EDS). Increasing the [Mg2+](i) from 0.2 to 2mM in the presence of cAMP-dependent protein kinase A significantly decreased I-CaL in LDS (70%) and in EDS (36%) CMs. In addition, the effect of forskolin was greatly attenuated in the presence of 2mM [Mg2+](i) in LDS but not in EDS CMs. The effect of forskolin was enhanced in the presence of ATP-gamma-S in LDS CMs compared with EDS CMs. The exposure of both EDS and LDS CMs to 2mM [Mg2+](i) considerably reduced the effects of iso-butylmethylxanthine (IBMX) and okadaic acid on I-CaL. Our results provide evidence for differential regulation of LTCCs activities by cytosolic Mg2+ concentration in developing cardiac cells and confirm that Mg2+ acts under conditions that favor opening of the LTCCs caused by channel phosphorylation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nguemo, Filomain UNSPECIFIED UNSPECIFIED UNSPECIFIED Semmler, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Reppel, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-435749
DOI:	10.1089/scd.2013.0549
Journal or Publication Title:	Stem Cells Dev.
Volume:	23
Number:	12
Page Range:	S. 1316 - 1328
Date:	2014
Publisher:	MARY ANN LIEBERT, INC
Place of Publication:	NEW ROCHELLE
ISSN:	1557-8534
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-ADRENERGIC STIMULATION; CA(V)1.2 CHANNELS; DEPENDENT INACTIVATION; DEVELOPMENTAL-CHANGES; PROTEIN PHOSPHATASE; CARDIAC MYOCYTES; CA2+ CURRENT; EF-HAND; VOLTAGE; MG2+ Multiple languages Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43574