Use of thapsigargin to study Ca2+ homeostasis in cardiac cells
Abstract
Several reports have documented that thapsigargin is a potent inhibitor of the SR Ca2+ ATPase isolated from cardiac or skeletal muscle. We have characterized the specificity of this agent in intact rat cardiac myocytes using cells maintained in the whole cell voltage clamp configuration. We have shown that thapsigargin decreases the magnitude of the Ca2+ transient and the twitch by about 80% while it slows the decay rate for these responses. These changes were not accompanied by any alterations in sarcolemmal currents or in the trigger Ca2+ generated by the inward calcium current. Taken together these results reveal that the action of thapsigargin is restricted to the SR Ca2+ ATPase in intact cardiac myocytes. Furthermore, it is demonstrated unambiguously that SR intracellular Ca2+ stores are an absolute requirement for the development of contractile tension in rat heart myocytes. It is shown that thapsigargin is a valuable probe to examine the importance of SR pools of Ca2+ and the role of the Ca2+ ATPase in intact myocytes as well as in genetically altered heart cells.
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Thapsigargin depletes ER Ca2+ stores by inhibiting the ER Ca2+-ATPase pump, preventing reuptake as Ca2+ passively leaks from the ER.
“Thapsigargin, an inhibitor of the ER Ca 2ϩ -ATPase pump, leads to the depletion of Ca 2ϩ stores because as Ca 2ϩ passively leaks from the ER, Ca 2ϩ levels are no longer balanced by reuptake (26).”
From Cch1 Restores Intracellular Ca2+ in Fungal Cells during Endoplasmic Reticulum Stress (2010) · cites this paper as [26]
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References 19 · Cited by 147
- Authors
- Rogers, T. B., Inesi, G., Wade, R., & Lederer, W. J.
- Affiliations
- University of Maryland, Baltimore (US)
- ORCID
- Lederer, W. J.
- Venue
- Bioscience Reports
- Publisher
- Portland Press Ltd.
- Published
- 1995-10-01
- Volume
- 15
- Issue
- 5
- Pages
- 341-349
- ISSN
- 0144-8463 (ISSN-L)
- 1573-4935
- OpenAlex
- W2011759169
- Cited by
- 147
- References
- 19
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 1 · 2022: 10 · 2021: 5 · 2020: 10 · 2019: 10 · 2018: 10 · 2017: 13 · 2016: 9 · 2015: 12 · 2014: 12 · 2013: 7 · 2012: 12
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioscience Reports (publishedVersion)
- PubMed (publishedVersion)
- 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
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- thapsigargin, sarcoplasmic reticulum Ca2+-ATPase, sarcoplasmic reticulum, calcium homeostasis, cardiomyocytes, calcium transients, Twitch, intracellular calcium stores, contractile tension, calcium inward current, whole-cell voltage clamp
- MeSH terms
- Calcium-Transporting ATPases, Animals, Calcium, Enzyme Inhibitors, Humans, Myocardium, Ion Transport, Thapsigargin
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