| Effects of FK-506 on contraction and Ca2+ transients in rat cardiac myocytes. | |
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MedLine Citation:
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PMID: 8943949 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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FK-506 binding protein (FKBP) has been reported to be closely associated with the ryanodine receptor in skeletal and cardiac muscle and to modulate sarcoplasmic reticulum (SR) Ca2+ release channel gating in isolated channels. FK-506 can inhibit the activity of FKBP, thereby reversing its effects on SR Ca2+ release. We investigated the function of FKBP during normal contractions and Ca2+ transients in intact rat ventricular myocytes loaded with fluorescent Ca2+ indicators. FK-506 significantly increased steady state twitch Ca2+ transients and contraction amplitudes even under conditions in which the SR Ca2+ load and Ca2+ current were unaltered, suggesting that FK-506 increases the fraction of SR Ca2+ released during excitation-contraction (E-C) coupling. Action potentials were somewhat prolonged, consistent with the larger Ca2+ transients causing greater inward Na(+)-Ca2+ exchange current. FK-506 did not affect SR Ca2+ uptake but modestly decreased Ca2+ extrusion via Na(+)-Ca2+ exchange in intact cells (although no effect on Na(+)-Ca2+ exchange was seen in sarcolemmal vesicles). In most cells, FK-506 caused an increase in SR Ca2+ content during steady state stimulation, as assessed by caffeine-induced contractures. This was probably due to the inhibition of Ca2+ efflux via Na(+)-Ca2+ exchange. FK-506 also accelerated the rest decay of SR Ca2+ content and increased the frequency of resting Ca2+ sparks about fourfold. The increase in frequency of these basic Ca2+ release events was not associated with changes in the amplitude or duration of the Ca2+ sparks. We conclude that FK-506 increases the fraction of SR Ca2+ released during normal twitches and enhances the rate of SR Ca2+ release during rest. FK-506 also inhibits Na(+)-Ca2+ exchange, although this effect may be indirect. These effects are consistent with an important SR-stabilizing effect of FKBP in intact rat ventricular myocytes. |
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Authors:
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E McCall; L Li; H Satoh; T R Shannon; L A Blatter; D M Bers |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation research Volume: 79 ISSN: 0009-7330 ISO Abbreviation: Circ. Res. Publication Date: 1996 Dec |
Date Detail:
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Created Date: 1997-01-02 Completed Date: 1997-01-02 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1110-21 Citation Subset: IM |
Affiliation:
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Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, Ill 60153, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism* Calcium Channels / metabolism Cells, Cultured Fluorescent Dyes Heart / physiology* Male Muscle Proteins / metabolism Myocardial Contraction / drug effects* Myocardium / metabolism* Rats Rats, Sprague-Dawley Ryanodine Receptor Calcium Release Channel Tacrolimus / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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HL-30077/HL/NHLBI NIH HHS; HL-51941/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channels; 0/Fluorescent Dyes; 0/Muscle Proteins; 0/Ryanodine Receptor Calcium Release Channel; 109581-93-3/Tacrolimus; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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