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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

TitleAutomaticity and conduction properties of bio-artificial pacemakers assessed in an in vitro monolayer model of neonatal rat ventricular myocytes
Authors
KeywordsAction potential
Automaticity
HCN
I f
I K1
Issue Date2010
PublisherOxford 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?
AbstractAims 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 Identifierhttp://hdl.handle.net/10722/134671
ISSN
2015 Impact Factor: 4.021
2015 SCImago Journal Rankings: 2.201
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthR01 HL72857
Hong Kong Research Grant CouncilHKU 763306M
HKU 7747/08M
HKU 776908M
CC Wong Stem Cell Fund
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 FieldValueLanguage
dc.contributor.authorChan, YCen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorSiu, CWen_HK
dc.contributor.authorWang, Ken_HK
dc.contributor.authorLi, RAen_HK
dc.date.accessioned2011-07-05T08:24:00Z-
dc.date.available2011-07-05T08:24:00Z-
dc.date.issued2010en_HK
dc.identifier.citationEuropace, 2010, v. 12 n. 8, p. 1178-1187en_HK
dc.identifier.issn1099-5129en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134671-
dc.description.abstractAims 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.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://europace.oxfordjournals.org/en_HK
dc.relation.ispartofEuropaceen_HK
dc.subjectAction potentialen_HK
dc.subjectAutomaticityen_HK
dc.subjectHCNen_HK
dc.subjectI fen_HK
dc.subjectI K1en_HK
dc.subject.meshAction Potentials - physiology-
dc.subject.meshBiological Clocks - physiology-
dc.subject.meshHeart Ventricles - cytology-
dc.subject.meshMyocytes, Cardiac - cytology - physiology-
dc.subject.meshPacemaker, Artificial-
dc.titleAutomaticity and conduction properties of bio-artificial pacemakers assessed in an in vitro monolayer model of neonatal rat ventricular myocytesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://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.emailChan, YC:yauchi@graduate.hku.hken_HK
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_HK
dc.identifier.emailSiu, CW:cwdsiu@hkucc.hku.hken_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityChan, YC=rp01502en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authoritySiu, CW=rp00534en_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/europace/euq120en_HK
dc.identifier.pmid20472688-
dc.identifier.pmcidPMC2910602-
dc.identifier.scopuseid_2-s2.0-77955208066en_HK
dc.identifier.hkuros182823-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955208066&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume12en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1178en_HK
dc.identifier.epage1187en_HK
dc.identifier.isiWOS:000280535800024-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectTransplantation of Bioengineered Human Embryonic Stem Cell-derived Cardiomyocytes with Mature Electrical Phenotype in Post-infarction Heart Failure Improves Cardiac Function Without Proarrhythmia-
dc.identifier.scopusauthoridChan, YC=7403676116en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridSiu, CW=7006550690en_HK
dc.identifier.scopusauthoridWang, K=35286098800en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK

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