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Article: Sarco/Endoplasmic Reticulum Ca2+-ATPase is a more effective calcium remover than Sodium-Calcium Exchanger in human embryonic stem cell-derived cardiomyocytes

TitleSarco/Endoplasmic Reticulum Ca2+-ATPase is a more effective calcium remover than Sodium-Calcium Exchanger in human embryonic stem cell-derived cardiomyocytes
Authors
KeywordsPluripotent stem cell-derived cardiomyocytes
engineered cardiac tissue
SERCA pump
pumpsodium/calcium exchanger
Issue Date2019
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/
Citation
American Journal of Physiology: Heart and Circulatory Physiology, 2019, Epub How to Cite?
AbstractHuman pluripotent stem cell (hPSCs)-derived ventricular (V) cardiomyocytes (CMs) display immature Ca2+-handing properties with smaller transient amplitudes and slower kinetics due to such differences in crucial Ca2+-handling proteins as the poor sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pumpbut robust Na-Ca exchanger (NCX) activities in human embryonic stem cell (ESC)-derived VCMs compared to adult. Despite their fundamental importance in excitation-contraction coupling, the relative contribution of SERCA and NCX to Ca2+-handling of hPSC-VCMs remains unexplored.We systematically altered the activities of SERCA and NCX in hESC-VCMs and their engineered micro-tissues, followed by examining the resultant phenotypic consequences. SERCA overexpression in hESC-VCMs shortened the decay of Ca2+transient at low frequencies (0.5Hz) without affecting the amplitude, SR Ca2+content and Ca2+ baseline. Interestingly, shRNA-based NCX suppression did not prolong the transient decay, indicating a compensatory response for Ca2+removal. Although hESC-VCMs and their derived microtissues exhibited negative frequency-transient/force responses, SERCA overexpression rendered them less negative at high frequencies (>2 Hz) by accelerating Ca2+sequestration. We conclude that forhESC-VCMs and their microtissues, SERCA, rather than NCX, is the main Ca2+remover during diastole; poor SERCA expression is the leading cause for immature negative-frequency/force responses, which can be partially reverted by forced expression. Combinatorial approach to mature calcium handling in hESC-VCMs may help shed further mechanistic insights.
Persistent Identifierhttp://hdl.handle.net/10722/277341
ISSN
2017 Impact Factor: 3.569
2015 SCImago Journal Rankings: 1.823

 

DC FieldValueLanguage
dc.contributor.authorLi, S-
dc.contributor.authorChopra, A-
dc.contributor.authorKeung, W-
dc.contributor.authorChan, C-
dc.contributor.authorCosta, KD-
dc.contributor.authorKong, CW-
dc.contributor.authorHajjar, RJ-
dc.contributor.authorChen, C-
dc.contributor.authorLi, R-
dc.date.accessioned2019-09-20T08:49:08Z-
dc.date.available2019-09-20T08:49:08Z-
dc.date.issued2019-
dc.identifier.citationAmerican Journal of Physiology: Heart and Circulatory Physiology, 2019, Epub-
dc.identifier.issn0363-6135-
dc.identifier.urihttp://hdl.handle.net/10722/277341-
dc.description.abstractHuman pluripotent stem cell (hPSCs)-derived ventricular (V) cardiomyocytes (CMs) display immature Ca2+-handing properties with smaller transient amplitudes and slower kinetics due to such differences in crucial Ca2+-handling proteins as the poor sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pumpbut robust Na-Ca exchanger (NCX) activities in human embryonic stem cell (ESC)-derived VCMs compared to adult. Despite their fundamental importance in excitation-contraction coupling, the relative contribution of SERCA and NCX to Ca2+-handling of hPSC-VCMs remains unexplored.We systematically altered the activities of SERCA and NCX in hESC-VCMs and their engineered micro-tissues, followed by examining the resultant phenotypic consequences. SERCA overexpression in hESC-VCMs shortened the decay of Ca2+transient at low frequencies (0.5Hz) without affecting the amplitude, SR Ca2+content and Ca2+ baseline. Interestingly, shRNA-based NCX suppression did not prolong the transient decay, indicating a compensatory response for Ca2+removal. Although hESC-VCMs and their derived microtissues exhibited negative frequency-transient/force responses, SERCA overexpression rendered them less negative at high frequencies (>2 Hz) by accelerating Ca2+sequestration. We conclude that forhESC-VCMs and their microtissues, SERCA, rather than NCX, is the main Ca2+remover during diastole; poor SERCA expression is the leading cause for immature negative-frequency/force responses, which can be partially reverted by forced expression. Combinatorial approach to mature calcium handling in hESC-VCMs may help shed further mechanistic insights.-
dc.languageeng-
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/-
dc.relation.ispartofAmerican Journal of Physiology: Heart and Circulatory Physiology-
dc.subjectPluripotent stem cell-derived cardiomyocytes-
dc.subjectengineered cardiac tissue-
dc.subjectSERCA pump-
dc.subjectpumpsodium/calcium exchanger-
dc.titleSarco/Endoplasmic Reticulum Ca2+-ATPase is a more effective calcium remover than Sodium-Calcium Exchanger in human embryonic stem cell-derived cardiomyocytes-
dc.typeArticle-
dc.identifier.emailKeung, W: wkeung@hku.hk-
dc.identifier.emailLi, R: ronaldli@hkucc.hku.hk-
dc.identifier.authorityKeung, W=rp01887-
dc.identifier.authorityChan, C=rp01311-
dc.identifier.authorityKong, CW=rp01563-
dc.identifier.authorityLi, R=rp01352-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajpheart.00540.2018-
dc.identifier.hkuros305870-
dc.publisher.placeUnited States-

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