Cellular basis of abnormal calcium transients of failing human ventricular myocytes
Abstract
Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca 2+ ] i . This study examined the respective roles of the L-type Ca 2+ current ( I Ca ), SR Ca 2+ uptake, storage and release, Ca 2+ transport via the Na + -Ca 2+ exchanger (NCX), and Ca 2+ buffering in the altered Ca 2+ transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control V m and measure I m , respectively, and Fluo-3 was used to measure [Ca 2+ ] i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca 2+ transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca 2+ uptake rates by the SR and the amount of Ca 2+ stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca 2+ removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca 2+ ] i , I Ca density, or cellular Ca 2+ buffering. However, Ca 2+ influx during the late portions of the action potential seems able to elevate [Ca 2+ ] i in F but not in NF myocytes. A reduction in the rate of net Ca 2+ uptake by the SR slows the decay of the Ca 2+ transient and reduces SR Ca 2+ stores. This leads to reduced SR Ca 2+ release, which induces additional Ca 2+ influx during the plateau phase of the action potential, further slowing the decay of the Ca 2+ transient. These changes can explain the defective Ca 2+ transients of the failing human ventricular myocyte.
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In rabbit ventricles, SERCA and NCX remove 70-74% and 23-28% of calcium, respectively, similar to human ventricles where SERCA removes 76% and NCX 24%.
“Rabbit ventricular SERCA and NCX systems are responsible for removing 70–74% and 23–28% of calcium, respectively (Bassani, et al., 1994; Puglisi, Bassani, Bassani, Amin, & Bers, 1996). These values are again similar to the relative activities of SERCA (76%) and NCX (24%) in human ventricles (Piacentino, et al., 2003).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Piacentino, et al., 2003
Calcium handling mechanisms are similar between canine and human: SERCA and NCX contributions to calcium removal are 73% and 27% in canine and estimated 76% and 24% in human.
“the relative contributions of SERCA and NCX to calcium removal in canine myocardium are 73% and 27% (Bers, 2001) and in human myocardium are estimated to be 76% and 24% (Piacentino, et al., 2003), respectively.”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Piacentino, et al., 2003
One study estimated that SERCA contributes approximately 81.5% of calcium removal during relaxation in sheep, close to the 76% in humans.
“One study estimated that SERCA contributes to approximately 81.5% of calcium removal during relaxation in sheep (Dibb, Rueckschloss, Eisner, Isenberg, & Trafford, 2004) which is close to the 76% responsibility in humans (Piacentino, et al., 2003).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Piacentino, et al., 2003
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- Authors
- Piacentino, V., Weber, C. R., Chen, X., Weisser-Thomas, J., Margulies, K. B., Bers, D. M., & Houser, S. R.
- Affiliations
- Loyola University Chicago (US)
- Venue
- Circulation Research
- Published
- 2003-04-04
- Volume
- 92
- Issue
- 6
- Pages
- 651-658
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2068613600
- Cited by
- 477
- References
- 44
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 13 · 2023: 14 · 2022: 20 · 2021: 17 · 2020: 21 · 2019: 19 · 2018: 18 · 2017: 15 · 2016: 19 · 2015: 27 · 2014: 28 · 2013: 22 · 2012: 31
- FWCI
- 17.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Temple University
- National Institutes of Health (5r01hl064098-03, HL33921, HL-30077)
- National Heart, Lung, and Blood Institute (R01HL061495, HL-33921, HL 61495, HL30077, HL64098)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- heart failure, calcium transients, ventricular myocytes, sarcoplasmic reticulum calcium uptake, sarcoplasmic reticulum calcium release, L-type calcium current, Na+/Ca2+ exchanger, intracellular calcium buffering, action potential plateau, intracellular calcium
- MeSH terms
- Action Potentials, Calcium-Transporting ATPases, Aged, Calcium, Electric Conductivity, Female, Heart Failure, Heart Ventricles, Humans, Male, Middle Aged, Myocardial Contraction, Sarcoplasmic Reticulum, Ion Transport, Patch-Clamp Techniques, Sodium-Calcium Exchanger, Calcium Signaling, Myocytes, Cardiac, Sarcoplasmic Reticulum Calcium-Transporting ATPases
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