Molecular composition and functional properties of f-channels in murine embryonic stem cell-derived pacemaker cells

Barbuti, Andrea; Crespi, Alessia; Capilupo, Daniela; Mazzocchi, Nausicaa; Baruscotti, Mirko; DiFrancesco, Dario

doi:10.1016/j.yjmcc.2008.12.001

Cited by 38 publications

(28 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the beating hESC-derived myocytes, I f has been recorded and HCN2 expression was detected . Consistently, the I f driven pacemaker activity has also been observed in mouse ESC-derived beating myocytes (Abi-Gerges et al, 2000;Qu et al, 2008;Barbuti et al, 2009). Not surprisingly, in hESC-derived beating cardiomyocytes, the inward rectifier K + current, I K1 , and Kir2.1 protein expression were barely detected .…”

Section: Stem Cell Derived Cardiomyocytessupporting

confidence: 66%

Biological Pacemaker – Main Ideas and Optimization

Yu¹,

Lin²

2011

Modern Pacemakers - Present and Future

View full text Add to dashboard Cite

Section: Stem Cell Derived Cardiomyocytessupporting

confidence: 66%

Biological Pacemaker – Main Ideas and Optimization

Yu¹,

Lin²

2011

Modern Pacemakers - Present and Future

View full text Add to dashboard Cite

“…Only HCN4 has been shown to be the specific marker of pacemaker cells; HCN4 is expressed in up to 80% of the SAN and is considered to be crucial for the initiation and control of beating activity of these cells [7]. However, previous studies also revealed that the HCN1, HCN2, and HCN3 isoforms are variably distributed in the SAN as well as in other cardiac regions and excitable tissues [28,30,31]. Additionally, there is a high variation of HCN isoform expression according to species.…”

Section: Discussionmentioning

confidence: 99%

Functional Expression and Regulation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (HCN) in Mouse iPS Cell-derived Cardiomyocytes afterUTF1-Neo Selection

Semmler

Lehmann

Pfannkuche

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: In vitro reprogramming of somatic cells holds great potential to serve as an autologous source of cells for tissue repair. However, major difficulties in achieving this potential include obtaining homogeneous and stable cells for transplantation. High electrical activity of cells such as cardiomyocytes (CMs) is crucial for both, safety and efficiency of cell replacement therapy. Moreover, the function of the cardiac pacemaker is controlled by the activities of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here we have examined changes in HCN gene expression and function during cardiomyogenesis. Methods: We differentiated murine iPS cells selected by an undifferentiated transcription factor 1 (UTF1) -promoter-driven G418 resistance to CMs in vitro and characterized them by RT-PCR, immunocytochemistry, and electrophysiology. Results: As key cardiac markers alpha-actinin and cardiac troponin T could be identified in derived CMs. Immunocytochemical staining of CMs showed the presence of all HCN subunits (HCN1-4). Electrophysiology experiments revealed developmental changes of action potentials and I_f currents as well as functional hormonal regulation and sensitivity to I_f channel blockers. Conclusion: We conclude that iPS cells derived from UTF-selection give rise to functional CMs in vitro, with established hormonal regulation pathways and functionally expressed I_f current in a development-dependent manner; and have all phenotypes with the pacemaker as predominant subtype. This might be of great importance for transplantation purposes.

show abstract

“…Embryonic stem cells differentiate in vitro into spontaneously beating multicellular cardiomyocyte clusters within embryoid bodies (EBs), while recapitulating developmental stages of embryonic cardiomyogenesis (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Thus, human embryonic stem cell-derived cardiomyocytes (hESC-CMs) may provide insights into the pacemaker mechanisms of embryonic cardiac development.…”

mentioning

confidence: 99%

SK4 Ca ²⁺ activated K ⁺ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells

Weisbrod

Peretz

Ziskind³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. Two main mechanisms have been proposed: (i) the "voltage-clock," where the hyperpolarizationactivated funny current I f causes diastolic depolarization that triggers action potential cycling; and (ii) the "Ca 2+ clock," where cyclical release of Ca 2+ from Ca 2+ stores depolarizes the membrane during diastole via activation of the Na + -Ca 2+ exchanger. Nonetheless, these mechanisms remain controversial. Here, we used human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to study their autonomous beating mechanisms. Combined current-and voltage-clamp recordings from the same cell showed the so-called "voltage and Ca 2+ clock" pacemaker mechanisms to operate in a mutually exclusive fashion in different cell populations, but also to coexist in other cells. Blocking the "voltage or Ca 2+ clock" produced a similar depolarization of the maximal diastolic potential (MDP) that culminated by cessation of action potentials, suggesting that they converge to a common pacemaker component. Using patch-clamp recording, realtime PCR, Western blotting, and immunocytochemistry, we identified a previously unrecognized Ca 2+ -activated intermediate K + conductance (IK Ca , KCa3.1, or SK4) in young and old stage-derived hESCCMs. IK Ca inhibition produced MDP depolarization and pacemaker suppression. By shaping the MDP driving force and exquisitely balancing inward currents during diastolic depolarization, IK Ca appears to play a crucial role in human embryonic cardiac automaticity.

show abstract

Molecular composition and functional properties of f-channels in murine embryonic stem cell-derived pacemaker cells

Cited by 38 publications

References 59 publications

Biological Pacemaker – Main Ideas and Optimization

Biological Pacemaker – Main Ideas and Optimization

Functional Expression and Regulation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (HCN) in Mouse iPS Cell-derived Cardiomyocytes afterUTF1-Neo Selection

SK4 Ca ²⁺ activated K ⁺ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells

Contact Info

Product

Resources

About

Molecular composition and functional properties of f-channels in murine embryonic stem cell-derived pacemaker cells

Cited by 38 publications

References 59 publications

Biological Pacemaker – Main Ideas and Optimization

Biological Pacemaker – Main Ideas and Optimization

Functional Expression and Regulation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (HCN) in Mouse iPS Cell-derived Cardiomyocytes afterUTF1-Neo Selection

SK4 Ca 2+ activated K + channel is a critical player in cardiac pacemaker derived from human embryonic stem cells

Contact Info

Product

Resources

About

SK4 Ca ²⁺ activated K ⁺ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells