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Article: Synergistic effects of inward rectifier (I K1) and pacemaker (I f) currents on the induction of bioengineered cardiac automaticity

TitleSynergistic effects of inward rectifier (I K1) and pacemaker (I f) currents on the induction of bioengineered cardiac automaticity
Authors
KeywordsAutomaticity
Bioartificial pacemaker
I f
I K1
Synergism
Issue Date2009
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1045-3873
Citation
Journal Of Cardiovascular Electrophysiology, 2009, v. 20 n. 9, p. 1048-1054 How to Cite?
AbstractSynergistic Effects of I K1 and I f Currents. Introduction: Normal heart rhythms originate in the sinoatrial node. HCN-encoded funny current (I f) and the Kir2-encoded inward rectifier (I K1) counteract each other by respectively oscillating and stabilizing the negative resting membrane potential, and controlling action potential firing. Therefore, I K1 suppression and I f overexpression have been independently exploited to convert cardiomyocytes (CMs) into AP-firing bioartificial pacemakers. Although the 2 strategies have been largely assumed synergistic, their complementarity has not been investigated. Methods and Results: We explored the interrelationships of automaticity, I f and I K1 by transducing single left ventricular (LV) CMs isolated from guinea pig hearts with the recombinant adenoviruses Ad-CMV-GFP-IRES-HCN1- ÄÄÄ and/or Ad-CGI-Kir2.1 to mediate their current densities via a whole-cell patch clamp technique at 37°C. Results showed that Ad-CGI-HCN1-ÄÄÄ but not Ad-CGI-Kir2.1 transduction induced automaticity (181.1 ± 13.1 bpm). Interestingly, Ad-CGI-HCN1- ÄÄÄ/Ad-CGI-Kir2.1 cotransduction significantly promoted the induced firing frequency (320.0 ± 15.8 bpm; P < 0.05). Correlation analysis revealed that the firing frequency, phase-4 slope and APD 90 of AP-firing LV CMs were correlated with I f (R 2 > 0.7) only when -2 >I K1 >-4 pA/pF but not with I K1 over the entire I f ranges examined (0.02 < R 2 < 0.4). Unlike I f, I K1 displayed correlation with neither the phase-4 slope (R 2 = 0.02) nor phase-4 length (R 2 = 0.04) when -2 > I f > -4 pA/pF. As anticipated, however, APD 90 was correlated with I K1 (R 2 = 0.4). Conclusion: We conclude that an optimal level of I K1 maintains a voltage range for I f to operate most effectively during a dynamic cardiac cycle. (J Cardiovasc Electrophysiol, Vol. 20, pp. 1048-1054) © 2009 Wiley Periodicals, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/91435
ISSN
2015 Impact Factor: 3.097
2015 SCImago Journal Rankings: 1.863
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
NIHR01 HL72857
University of California
Hong Kong Research Grant CouncilHKU 7459/04M
Croucher Foundation
Funding Information:

This work was supported by grants from the NIH (R01 HL72857 to R. A. Li), the Stem Cell Program of the University of California (to R. A. Li), and the Hong Kong Research Grant Council (HKU 7459/04M to C. P. Lau, H. F. Tse, and R. A. Li). C. W. Siu was supported by a postdoctoral fellowship award from the Croucher Foundation.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChan, YCen_HK
dc.contributor.authorSiu, CWen_HK
dc.contributor.authorLau, YMen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorLi, RAen_HK
dc.contributor.authorTse, HFen_HK
dc.date.accessioned2010-09-17T10:19:22Z-
dc.date.available2010-09-17T10:19:22Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Cardiovascular Electrophysiology, 2009, v. 20 n. 9, p. 1048-1054en_HK
dc.identifier.issn1045-3873en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91435-
dc.description.abstractSynergistic Effects of I K1 and I f Currents. Introduction: Normal heart rhythms originate in the sinoatrial node. HCN-encoded funny current (I f) and the Kir2-encoded inward rectifier (I K1) counteract each other by respectively oscillating and stabilizing the negative resting membrane potential, and controlling action potential firing. Therefore, I K1 suppression and I f overexpression have been independently exploited to convert cardiomyocytes (CMs) into AP-firing bioartificial pacemakers. Although the 2 strategies have been largely assumed synergistic, their complementarity has not been investigated. Methods and Results: We explored the interrelationships of automaticity, I f and I K1 by transducing single left ventricular (LV) CMs isolated from guinea pig hearts with the recombinant adenoviruses Ad-CMV-GFP-IRES-HCN1- ÄÄÄ and/or Ad-CGI-Kir2.1 to mediate their current densities via a whole-cell patch clamp technique at 37°C. Results showed that Ad-CGI-HCN1-ÄÄÄ but not Ad-CGI-Kir2.1 transduction induced automaticity (181.1 ± 13.1 bpm). Interestingly, Ad-CGI-HCN1- ÄÄÄ/Ad-CGI-Kir2.1 cotransduction significantly promoted the induced firing frequency (320.0 ± 15.8 bpm; P < 0.05). Correlation analysis revealed that the firing frequency, phase-4 slope and APD 90 of AP-firing LV CMs were correlated with I f (R 2 > 0.7) only when -2 >I K1 >-4 pA/pF but not with I K1 over the entire I f ranges examined (0.02 < R 2 < 0.4). Unlike I f, I K1 displayed correlation with neither the phase-4 slope (R 2 = 0.02) nor phase-4 length (R 2 = 0.04) when -2 > I f > -4 pA/pF. As anticipated, however, APD 90 was correlated with I K1 (R 2 = 0.4). Conclusion: We conclude that an optimal level of I K1 maintains a voltage range for I f to operate most effectively during a dynamic cardiac cycle. (J Cardiovasc Electrophysiol, Vol. 20, pp. 1048-1054) © 2009 Wiley Periodicals, Inc.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1045-3873en_HK
dc.relation.ispartofJournal of Cardiovascular Electrophysiologyen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectAutomaticityen_HK
dc.subjectBioartificial pacemakeren_HK
dc.subjectI fen_HK
dc.subjectI K1en_HK
dc.subjectSynergismen_HK
dc.subject.meshAction potentials - physiology-
dc.subject.meshCyclic nucleotide-gated cation channels - genetics-
dc.subject.meshGenetic engineering - methods-
dc.subject.meshHeart conduction system - physiology-
dc.subject.meshIon channel gating - physiology-
dc.titleSynergistic effects of inward rectifier (I K1) and pacemaker (I f) currents on the induction of bioengineered cardiac automaticityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1045-3873&volume=20&issue=9&spage=1048&epage=1054&date=2009&atitle=Synergistic+effects+of+Inward+Rectifier+(IK1)+and+Pacemaker+(If)+Currents+on+the+Induction+of+Bioengineered+Cardiac+Automaticity-
dc.identifier.emailChan, YC:yauchi@graduate.hku.hken_HK
dc.identifier.emailSiu, CW:cwdsiu@hkucc.hku.hken_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_HK
dc.identifier.authorityChan, YC=rp01502en_HK
dc.identifier.authoritySiu, CW=rp00534en_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1540-8167.2009.01475.xen_HK
dc.identifier.pmid19460073-
dc.identifier.pmcidPMC2739246-
dc.identifier.scopuseid_2-s2.0-69249189526en_HK
dc.identifier.hkuros182843-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-69249189526&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume20en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1048en_HK
dc.identifier.epage1054en_HK
dc.identifier.isiWOS:000269369400015-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectFunctional role of pacemaker current, I(f) in sinoatrial node probed by somatic gene transfer of bioengineered HCN channels in swine-
dc.identifier.scopusauthoridChan, YC=7403676116en_HK
dc.identifier.scopusauthoridSiu, CW=7006550690en_HK
dc.identifier.scopusauthoridLau, YM=35102601300en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.citeulike5706426-

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