ArticleThe Journal of physiology2009
Coupling an HCN2-expressing cell to a myocyte creates a two-cell pacing unit.
Article in The Journal of physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Mechanisms of rectified gap junctional coupling enhancing pacemaking activity of biologically engineered pacemaker cells.NPJ systems biology and applications · 2026Article
- Intercellular delivery of therapeutic oligonucleotides.Journal of drug delivery science and technology · 2022Article
- Integration of Engineered "Spark-Cell" Spheroids for Optical Pacing of Cardiac Tissue.Frontiers in bioengineering and biotechnology · 2021Article
- Biological pacemaker: from biological experiments to computational simulation.Journal of Zhejiang University. Science. B · 2020Review
- A study of the outward background current conductance gPflugers Archiv : European journal of physiology · 2020Article
- Toward Biological Pacing by Cellular Delivery of Hcn2/SkM1.Frontiers in physiology · 2020Article
- Cardiomyocyte Progenitor Cells as a Functional Gene Delivery Vehicle for Long-Term Biological Pacing.Molecules (Basel, Switzerland) · 2019Article
- Review
- Transcription factor Tbx18 induces the differentiation of c-kitAmerican journal of translational research · 2018Article
- Article
- The Dome Wall of Bladder Acts as a Pacemaker Site in Detrusor Instability in Rats.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Relevance of HCN2-expressing human mesenchymal stem cells for the generation of biological pacemakers.Stem cell research & therapy · 2016Article
- A comparison of two cellular delivery mechanisms for small interfering RNA.Physiological reports · 2015Article
- Stem cell-based biological pacemakers from proof of principle to therapy: a review.Cytotherapy · 2014Review
- MATLAB implementation of a dynamic clamp with bandwidth of >125 kHz capable of generating I Na at 37 °C.Pflugers Archiv : European journal of physiology · 2013Article
- Genetic engineering of somatic cells to study and improve cardiac function.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2012Article
- Size and ionic currents of unexcitable cells coupled to cardiomyocytes distinctly modulate cardiac action potential shape and pacemaking activity in micropatterned cell pairs.Circulation. Arrhythmia and electrophysiology · 2012Article
- Effect of skeletal muscle Na(+) channel delivered via a cell platform on cardiac conduction and arrhythmia induction.Circulation. Arrhythmia and electrophysiology · 2012Article
- Stimulating cardiac muscle by light: cardiac optogenetics by cell delivery.Circulation. Arrhythmia and electrophysiology · 2011Article
- The road to biological pacing.Nature reviews. Cardiology · 2011Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We examined whether coupling of a ventricular myocyte to a non-myocyte cell expressing HCN2 could create a two-cell syncytium capable of generating sustained pacing. Three non-myocyte cell types were transfected with the mHCN2 gene and used as sources of mHCN2-induced currents. They were human mesenchymal stem cells and HEK293 cells, both of which express connexin43 (Cx43), and HeLa cells transfected with Cx43. Cell-cell coupling between heterologous pairs increased with time in co-culture, and hyperpolarization of the myocyte induced HCN2 currents, indicating current transfer from the mHCN2-expressing cell to the myocyte via gap junctions. The magnitude of the HCN2 currents recorded in myocytes increased with increasing junctional conductance. Once a critical level of electrical cell-cell coupling between myocytes and mHCN2 transfected cells was exceeded spontaneous action potentials were generated at frequencies of approximately 0.6 to 1.7 Hz (1.09 +/- 0.05 Hz). Addition of carbenoxolone (200 microM), a gap junction channel blocker, to the media stopped spontaneous activity in heterologous cell pairs. Carbenoxolone washout restored activity. Blockade of HCN2 currents by 100 microM 9-amino-1,2,3,4-tetrahydroacridine (THA) stopped spontaneous activity and subsequent washout restored it. Neither THA nor carbenoxolone affected electrically stimulated action potentials in isolated single myocytes. In summary, the inward current evoked in the genetically engineered (HCN2-expressing) cell was delivered to the cardiac myocyte via gap junctions and generated action potentials such that the cell pair could function as a pacemaker unit. This finding lays the groundwork for understanding cell-based biological pacemakers in vivo once an understanding of delivery and target cell geometry is defined.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.