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Cited by 283

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes

Open access
Satin, Jonathan, Kehat, Izhak, Caspi, Oren, Huber, Irit, Arbel, Gil, Itzhaki, Ilanit, Magyar, Janos, Schroder, Elizabeth A., Perlman, Ido, Gepstein, Lior·2004·The Journal of Physiology
DOI 10.1113/jphysiol.2004.068213
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Abstract

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 μ m) dramatically slowed conduction velocity from 5.1 to 3.2 cm s−1 while 100 μ m TTX caused complete cessation of spontaneous electrical activity in all EBs studied. In contrast, the Ca 2+ channel blockers nifedipine or diltiazem (1 μ 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 μ m TTX induced longer AP interpulse intervals and 10 μ m TTX caused cessation of spontaneous APs. In contrast nifedipine (Ca 2+ channel block) and 2 m m Cs+ (HCN complete block) induced shorter AP interpulse intervals. In single cells, APs stimulated by current pulses had a maximum upstroke velocity (d V/d tmax) of 118 ± 14 V s−1 in control conditions; in contrast, partial block of Na+ current significantly reduced stimulated d V/d tmax (38 ± 15 V s−1). RT‐PCR revealed Na V 1.5, Ca V 1.2, 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 Na V 1.5; thus, the Na V 1.5 Na+ channel is important for initiating spontaneous excitability in hES‐derived heart cells.

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Metadata

Authors
Satin, J., Kehat, I., Caspi, O., Huber, I., Arbel, G., Itzhaki, I., Magyar, J., Schroder, E. A., Perlman, I., & Gepstein, L.
Venue
The Journal of Physiology
Publisher
Wiley
Published
2004-08-25
Volume
559
Issue
2
Pages
479-496
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.2004.068213
OpenAlex
W1530324520
Cited by
283
References
36
FWCI
10.53
Type
journal article
Language
en
Open access
green

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