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- Publisher Website: 10.1093/europace/euq120
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- PMID: 20472688
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Article: Automaticity and conduction properties of bio-artificial pacemakers assessed in an in vitro monolayer model of neonatal rat ventricular myocytes
Title | Automaticity and conduction properties of bio-artificial pacemakers assessed in an in vitro monolayer model of neonatal rat ventricular myocytes | ||||||||
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Authors | |||||||||
Keywords | Action potential Automaticity HCN I f I K1 | ||||||||
Issue Date | 2010 | ||||||||
Publisher | Oxford University Press. The Journal's web site is located at http://europace.oxfordjournals.org/ | ||||||||
Citation | Europace, 2010, v. 12 n. 8, p. 1178-1187 How to Cite? | ||||||||
Abstract | Aims A better understanding of the ionic mechanisms for cardiac automaticity can lead to better strategies for engineering bio-artificial pacemakers. Here, we attempted to better define the relative contribution of I f and I K1 in the generation of spontaneous action potentials (SAPs) in cardiomyocytes (CMs). Methods and results Monolayers of neonatal rat ventricular myocytes (NRVMs) were transduced with a recombinant adenovirus (Ad) to express a gating-engineered HCN1 construct (HCN1-ΔΔΔ) for patch-clamp and multielectrode array (MEA) recordings. Single NRVMs exhibited a bi-phasic response in the generation of SAPs (62.6 ± 17.4 b.p.m., Days 1-2; 194.3 ± 12.3 b.p.m., Days 3-4; 73 quiescent, Days 9-10). Although automaticity time-dependently decreased and subsequently ceased, If remained fairly stable (-5.2 ± 1.1 pA/pF, Days 1-2;-5.1 ± 1.4 pA/pF, Days 7-8;-4.3 ± 1.3 pA/pF, Days 13-14). In contrast, I K1 declined rapidly (from-16.9 ± 2.7 pA/pF on Days 1-2 to-4.4 ± 1.6 pA/pF on Days 5-6). Maximum diastolic potential/resting membrane potential (r = 0.89) and action potential duration at 50 (APD50, r = 0.73) and 90 (APD90, r = 0.75) but not the firing rate (r =-0.3) were positively correlated to the I K1. Similarly, monolayer NRVMs ceased to spontaneously fire after long-term culture. Ad-HCN1-ΔΔΔ transduction restored pacing in silenced individual and monolayer NRVMs but with reduced conduction velocity and field potential amplitude. Conclusion We conclude that the combination of I K1 and I f primes CMs for bio-artificial pacing by determining the threshold. However, I f functions as a membrane potential oscillator to determine the basal firing frequency. Future engineering of automaticity in the multicellular setting needs to have conduction taken into consideration. Published on behalf of the European Society of Cardiology. © The Author 2010. | ||||||||
Persistent Identifier | http://hdl.handle.net/10722/134671 | ||||||||
ISSN | 2023 Impact Factor: 7.9 2023 SCImago Journal Rankings: 2.895 | ||||||||
PubMed Central ID | |||||||||
ISI Accession Number ID |
Funding Information: This work was supported by grants from the National Institutes of Health (R01 HL72857 to R.A.L.), the Hong Kong Research Grant Council General Research Fund (HKU 763306M, HKU 7747/08M and HKU 776908M to C.W.S., H.F.T., and R.A.L.), and the CC Wong Stem Cell Fund (to H.F. T. and R.A.L.). | ||||||||
References | |||||||||
Grants |
DC Field | Value | Language |
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dc.contributor.author | Chan, YC | en_HK |
dc.contributor.author | Tse, HF | en_HK |
dc.contributor.author | Siu, CW | en_HK |
dc.contributor.author | Wang, K | en_HK |
dc.contributor.author | Li, RA | en_HK |
dc.date.accessioned | 2011-07-05T08:24:00Z | - |
dc.date.available | 2011-07-05T08:24:00Z | - |
dc.date.issued | 2010 | en_HK |
dc.identifier.citation | Europace, 2010, v. 12 n. 8, p. 1178-1187 | en_HK |
dc.identifier.issn | 1099-5129 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/134671 | - |
dc.description.abstract | Aims A better understanding of the ionic mechanisms for cardiac automaticity can lead to better strategies for engineering bio-artificial pacemakers. Here, we attempted to better define the relative contribution of I f and I K1 in the generation of spontaneous action potentials (SAPs) in cardiomyocytes (CMs). Methods and results Monolayers of neonatal rat ventricular myocytes (NRVMs) were transduced with a recombinant adenovirus (Ad) to express a gating-engineered HCN1 construct (HCN1-ΔΔΔ) for patch-clamp and multielectrode array (MEA) recordings. Single NRVMs exhibited a bi-phasic response in the generation of SAPs (62.6 ± 17.4 b.p.m., Days 1-2; 194.3 ± 12.3 b.p.m., Days 3-4; 73 quiescent, Days 9-10). Although automaticity time-dependently decreased and subsequently ceased, If remained fairly stable (-5.2 ± 1.1 pA/pF, Days 1-2;-5.1 ± 1.4 pA/pF, Days 7-8;-4.3 ± 1.3 pA/pF, Days 13-14). In contrast, I K1 declined rapidly (from-16.9 ± 2.7 pA/pF on Days 1-2 to-4.4 ± 1.6 pA/pF on Days 5-6). Maximum diastolic potential/resting membrane potential (r = 0.89) and action potential duration at 50 (APD50, r = 0.73) and 90 (APD90, r = 0.75) but not the firing rate (r =-0.3) were positively correlated to the I K1. Similarly, monolayer NRVMs ceased to spontaneously fire after long-term culture. Ad-HCN1-ΔΔΔ transduction restored pacing in silenced individual and monolayer NRVMs but with reduced conduction velocity and field potential amplitude. Conclusion We conclude that the combination of I K1 and I f primes CMs for bio-artificial pacing by determining the threshold. However, I f functions as a membrane potential oscillator to determine the basal firing frequency. Future engineering of automaticity in the multicellular setting needs to have conduction taken into consideration. Published on behalf of the European Society of Cardiology. © The Author 2010. | en_HK |
dc.language | eng | en_US |
dc.publisher | Oxford University Press. The Journal's web site is located at http://europace.oxfordjournals.org/ | en_HK |
dc.relation.ispartof | Europace | en_HK |
dc.subject | Action potential | en_HK |
dc.subject | Automaticity | en_HK |
dc.subject | HCN | en_HK |
dc.subject | I f | en_HK |
dc.subject | I K1 | en_HK |
dc.subject.mesh | Action Potentials - physiology | - |
dc.subject.mesh | Biological Clocks - physiology | - |
dc.subject.mesh | Heart Ventricles - cytology | - |
dc.subject.mesh | Myocytes, Cardiac - cytology - physiology | - |
dc.subject.mesh | Pacemaker, Artificial | - |
dc.title | Automaticity and conduction properties of bio-artificial pacemakers assessed in an in vitro monolayer model of neonatal rat ventricular myocytes | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1099-5129&volume=12&issue=8&spage=1178&epage=1187&date=2010&atitle=Automaticity+and+conduction+properties+of+bio-artificial+pacemakers+assessed+in+an+in+vitro+monolayer+model+of+neonatal+rat+ventricular+myocytes | - |
dc.identifier.email | Chan, YC:yauchi@graduate.hku.hk | en_HK |
dc.identifier.email | Tse, HF:hftse@hkucc.hku.hk | en_HK |
dc.identifier.email | Siu, CW:cwdsiu@hkucc.hku.hk | en_HK |
dc.identifier.email | Li, RA:ronaldli@hkucc.hku.hk | en_HK |
dc.identifier.authority | Chan, YC=rp01502 | en_HK |
dc.identifier.authority | Tse, HF=rp00428 | en_HK |
dc.identifier.authority | Siu, CW=rp00534 | en_HK |
dc.identifier.authority | Li, RA=rp01352 | en_HK |
dc.description.nature | link_to_OA_fulltext | en_US |
dc.identifier.doi | 10.1093/europace/euq120 | en_HK |
dc.identifier.pmid | 20472688 | - |
dc.identifier.pmcid | PMC2910602 | - |
dc.identifier.scopus | eid_2-s2.0-77955208066 | en_HK |
dc.identifier.hkuros | 182823 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-77955208066&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 12 | en_HK |
dc.identifier.issue | 8 | en_HK |
dc.identifier.spage | 1178 | en_HK |
dc.identifier.epage | 1187 | en_HK |
dc.identifier.isi | WOS:000280535800024 | - |
dc.publisher.place | United Kingdom | en_HK |
dc.relation.project | Transplantation of Bioengineered Human Embryonic Stem Cell-derived Cardiomyocytes with Mature Electrical Phenotype in Post-infarction Heart Failure Improves Cardiac Function Without Proarrhythmia | - |
dc.identifier.scopusauthorid | Chan, YC=7403676116 | en_HK |
dc.identifier.scopusauthorid | Tse, HF=7006070805 | en_HK |
dc.identifier.scopusauthorid | Siu, CW=7006550690 | en_HK |
dc.identifier.scopusauthorid | Wang, K=35286098800 | en_HK |
dc.identifier.scopusauthorid | Li, RA=7404724466 | en_HK |
dc.identifier.issnl | 1099-5129 | - |