| Refractoriness of sarcoplasmic reticulum Ca2+ release determines Ca2+ alternans in atrial myocytes. | |
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MedLine Citation:
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PMID: 22467301 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiac alternans is a recognized risk factor for cardiac arrhythmia and sudden cardiac death. At the cellular level, Ca(2+) alternans appears as cytosolic Ca(2+) transients of alternating amplitude at regular beating frequency. Cardiac alternans is a multifactorial process but has been linked to disturbances in intracellular Ca(2+) regulation. In atrial myocytes, we tested the role of voltage-gated Ca(2+) current, sarcoplasmic reticulum (SR) Ca(2+) load, and restitution properties of SR Ca(2+) release for the occurrence of pacing-induced Ca(2+) alternans. Voltage-clamp experiments revealed that peak Ca(2+) current was not affected during alternans, and alternans of end-diastolic SR Ca(2+) load, evaluated by application of caffeine or measured directly with an intra-SR fluorescent Ca(2+) indicator (fluo-5N), were not a requirement for cytosolic Ca(2+) alternans. Restitution properties and kinetics of refractoriness of Ca(2+) release after activation during alternans were evaluated by four different approaches: measurements of 1) the delay (latency) of occurrence of spontaneous global Ca(2+) releases and 2) Ca(2+) spark frequency, both during rest after a large and small alternans Ca(2+) transient; 3) the magnitude of premature action potential-induced Ca(2+) transients after a large and small beat; and 4) the efficacy of a photolytically induced Ca(2+) signal (Ca(2+) uncaging from DM-nitrophen) to trigger additional Ca(2+) release during alternans. The results showed that the latency of global spontaneous Ca(2+) release was prolonged and Ca(2+) spark frequency was decreased after the large Ca(2+) transient during alternans. Furthermore, the restitution curve of the Ca(2+) transient elicited by premature action potentials or by photolysis-induced Ca(2+) release from the SR lagged behind after a large-amplitude transient during alternans compared with the small-amplitude transient. The data demonstrate that beat-to-beat alternation of the time-dependent restitution properties and refractory kinetics of the SR Ca(2+) release mechanism represents a key mechanism underlying cardiac alternans. |
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Authors:
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Vyacheslav M Shkryl; Joshua T Maxwell; Timothy L Domeier; Lothar A Blatter |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-03-30 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 302 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-06-04 Completed Date: 2012-09-12 Revised Date: 2013-06-12 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2310-20 Citation Subset: IM |
Affiliation:
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Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, Illinois 60612, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials
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physiology Animals Calcium / metabolism* Cardiac Pacing, Artificial Models, Animal Myocytes, Cardiac / cytology, metabolism* Patch-Clamp Techniques Rabbits Refractory Period, Electrophysiological / physiology* Sarcoplasmic Reticulum / metabolism* Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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F32 HL090211/HL/NHLBI NIH HHS; HL-101235/HL/NHLBI NIH HHS; HL-62231/HL/NHLBI NIH HHS; HL-80101/HL/NHLBI NIH HHS; R01 HL062231-15/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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