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001-es BibID:	BIBFORM032929
Első szerző:	Satin, Jonathan
Cím:	Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes / Jonathan Satin, Izhak Kehat, Oren Caspi, Irit Huber, Gil Arbel, Ilanit Itzhaki, Janos Magyar, Elizabeth A. Schroder, Ido Perlman, Lior Gepstein
Dátum:	2004
ISSN:	0022-3751
Megjegyzések:	Human embryonic stem cell-derived cardiomyocytes (hES-CMs) are thought to recapitulate the embryonic development of heart cells. Given the exciting potential of hES-CMs as replacement tissue in diseased hearts, we investigated the pharmacological sensitivity and ionic current of mid-stage hES-CMs (20?35 days post plating). A high-resolution microelectrode array was used to assess conduction in multicellular preparations of hES-CMs in spontaneously contracting embryoid bodies (EBs). TTX (10 ?m) dramatically slowed conduction velocity from 5.1 to 3.2 cm s?1 while 100 ?m TTX caused complete cessation of spontaneous electrical activity in all EBs studied. In contrast, the Ca2+ channel blockers nifedipine or diltiazem (1 ?m) had a negligible effect on conduction. These results suggested a prominent Na+ channel current, and therefore we patch-clamped isolated cells to record Na+ current and action potentials (APs). We found for isolated hES-CMs a prominent Na+ current (244 ? 42 pA pF?1 at 0 mV; n = 19), and a hyperpolarization-activated current (HCN), but no inward rectifier K+ current. In cell clusters, 3 ?m TTX induced longer AP interpulse intervals and 10 ?m TTX caused cessation of spontaneous APs. In contrast nifedipine (Ca2+ channel block) and 2 mm Cs+ (HCN complete block) induced shorter AP interpulse intervals. In single cells, APs stimulated by current pulses had a maximum upstroke velocity (dV/dtmax) of 118 ? 14 V s?1 in control conditions; in contrast, partial block of Na+ current significantly reduced stimulated dV/dtmax (38 ? 15 V s?1). RT-PCR revealed NaV1.5, CaV1.2, and HCN-2 expression but we could not detect Kir2.1. We conclude that hES-CMs at mid-range development express prominent Na+ current. The absence of background K+ current creates conditions for spontaneous activity that is sensitive to TTX in the same range of partial block of NaV1.5; thus, the NaV1.5 Na+ channel is important for initiating spontaneous excitability in hES-derived heart cells.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Journal of Physiology (London) 559 : 2 (2004), p. 479-496. -
További szerzők:	Kehat, Izhak Caspi, Oren Huber, Irit Arbel, Gil Itzhaki, Ilanit Magyar János (1961-) (élettanász) Schroder, Elizabeth Perlman, Ido Gepstein, Lior
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM032937
035-os BibID:	PMID:17158651
Első szerző:	Schroder, Elizabeth
Cím:	Chronic verapamil treatment remodels ICa,L in mouse ventricle / Elizabeth Schroder, Janos Magyar, Don Burgess, Douglas Andres, Jonathan Satin
Dátum:	2007
ISSN:	0363-6135
Megjegyzések:	In this study we tested the hypothesis that ventricular homeostasis of L-type Ca(2+) current (I(Ca,L)) minimally involves regulation of the main pore-forming alpha-subunit (Ca(V)1.2) and auxiliary proteins that serve as positive or negative regulators of I(Ca,L). We treated animals for 24 h with verapamil (Ver, 3.6 mg.kg(-1).day(-1)), isoproterenol (Iso, 30 mg.kg(-1).day(-1)), or Iso + Ver via osmotic minipumps. To test for alterations of Ca(2+) channel complex components we performed real-time PCR and Western blot analysis on ventricle. In addition, cardiac myocytes (CMs) were dispersed and current was recorded in the whole cell configuration to evaluate I(Ca,L). Surprisingly, 24- to 48-h Ver increased Ca(V)1.2 mRNA and protein and I(Ca,L) current (Ver 11 +/- 1pA/pF vs. control 7 +/- 0.5pA/pF; P < 0.01). I(Ca,L) from CMs in Ver mice showed no change in whole cell capacitance. To examine the in vivo effects of a physiologically relevant Ca(2+) channel agonist, we treated mice with Iso. Twenty-four-hour Iso infusion increased heart rate; Ca(V)1.2- and Ca(V)beta(2) mRNA levels were constant, but the Ca(2+) channel subunit mRNA Rem was increased twofold. Cells isolated from 24-h Iso hearts showed no change in basal I(Ca,L) density and diminished responsiveness to acute 1 muM Iso. To further examine the homeostatic regulation of the Ca(2+) channel, we treated animals for 24 h with Iso + Ver. The influence of Iso + Ver was similar that of to Iso alone on Ca(2+) channel mRNAs and I(Ca,L), with the exception that it prevented the increase in Rem seen with Iso treatment. Long-term Ca(2+) channel blockade induces an increase of Ca(V)1.2 mRNA and protein and significantly increases I(Ca,L).
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	American Journal of Physiology-Heart And Circulatory Physiology 292 : 4 (2007), p. H1906-H1916. -
További szerzők:	Magyar János (1961-) (élettanász) Burgess, Don E. Andres, Douglas Satin, Jonathan
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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