title: Luminal Ca(2+) content regulates intracellular Ca(2+) release in subepicardial myocytes of intact beating mouse hearts: effect of exogenous buffers.
abstract: Ca(+)-induced Ca(2+) release tightly controls the function of ventricular cardiac myocytes under normal and pathological conditions. Two major factors contributing to the regulation of Ca(2+) release are the cytosolic free Ca(2+) concentration and sarcoplasmic reticulum (SR) Ca(2+) content. We hypothesized that the amount of Ca(2+) released from the SR during each heart beat strongly defines the refractoriness of Ca(2+) release. To test this hypothesis, EGTA AM, a high-affinity, slow-association rate Ca(2+) chelator, was used as a tool to modify luminal SR Ca(2+) content. An analysis of the cytosolic and luminal SR Ca(2+) dynamics recorded from the epicardial layer of intact mouse hearts indicated that the presence of EGTA reduced the diastolic SR free Ca(2+) concentration and fraction of SR Ca(2+) depletion during each beat. In addition, this maneuver shortened the refractory period and accelerated the restitution of Ca(2+) release. As a consequence of the accelerated restitution, the frequency dependence of Ca(2+) alternans was significantly shifted toward higher heart rates, suggesting a role of luminal SR Ca(2+) in the genesis of this highly arrhythmogenic phenomenon. Thus, intra-SR Ca(2+) dynamics set the refractoriness and frequency dependence of Ca(2+) transients in subepicardial ventricular myocytes.
authors.affiliation: School of Engineering, Univ. of California-Merced, 5200 N. Lake Rd., Merced, CA 95343, USA.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Kornyeyev
authors.forename: Mariano
authors.initials: M
authors.lastname: Reyes
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Escobar
mesh_terms: D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D023421:Models, Animal; D008962:Models, Theoretical; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010496:Pericardium / Q000166:cytology / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
chemical_list: D002021:Buffers; D004533:Egtazic Acid; C046770:EGTA acetoxymethyl ester; D002118:Calcium
references.citation: Biophys J. 2003 Aug;85(2):1080-97
references.pmid: 12885654
references.citation: Biophys J. 1996 May;70(5):2110-9
references.pmid: 9172735
references.citation: Biophys J. 2009 Oct 7;97(7):1864-72
references.pmid: 19804716
references.citation: Biophys J. 2004 Apr;86(4):2121-8
references.pmid: 15041652
references.citation: J Physiol. 2002 Nov 15;545(1):65-79
references.pmid: 12433950
references.citation: Biophys J. 1994 Jun;66(6):1879-86
references.pmid: 8075325
references.citation: Proc R Soc Lond B Biol Sci. 1981 Mar 6;211(1183):205-35
references.pmid: 6111797
references.citation: J Gen Physiol. 2008 Apr;131(4):325-34
references.pmid: 18347081
references.citation: Pflugers Arch. 1997 Sep;434(5):615-31
references.pmid: 9242727
references.citation: Circ Res. 2002 Sep 6;91(5):414-20
references.pmid: 12215490
references.citation: Biophys J. 2000 Jan;78(1):164-73
references.pmid: 10620283
references.citation: Circ Res. 1988 Jan;62(1):116-26
references.pmid: 2826039
references.citation: J Biol Chem. 1995 Mar 3;270(9):4361-7
references.pmid: 7876199
references.citation: Front Biosci. 2002 Jun 01;7:d1454-63
references.pmid: 12045014
references.citation: J Mol Biol. 1965 May;12:88-118
references.pmid: 14343300
references.citation: Cell Calcium. 1992 Mar;13(3):183-92
references.pmid: 1315621
references.citation: J Electrocardiol. 2003;36 Suppl:75-81
references.pmid: 14716596
references.citation: Exp Physiol. 2005 Jan;90(1):3-12
references.pmid: 15572459
references.citation: J Physiol. 2000 Apr 15;524 Pt 2:415-22
references.pmid: 10766922
references.citation: J Gen Physiol. 2004 May;123(5):533-53
references.pmid: 15111644
references.citation: Am J Physiol. 1995 Jan;268(1 Pt 1):C271-7
references.pmid: 7840156
references.citation: Am J Physiol Cell Physiol. 2001 Dec;281(6):C2049-60
references.pmid: 11698264
references.citation: J Mol Cell Cardiol. 2005 Sep;39(3):419-28
references.pmid: 16026799
references.citation: J Biol Chem. 1998 Oct 23;273(43):28470-7
references.pmid: 9774476
references.citation: J Physiol. 2000 Jun 1;525 Pt 2:483-98
references.pmid: 10835049
references.citation: J Biol Chem. 1989 Jan 15;264(2):1329-35
references.pmid: 2463249
references.citation: Heart Rhythm. 2007 Jul;4(7):964-72
references.pmid: 17599687
references.citation: Pflugers Arch. 2003 Mar;445(6):747-58
references.pmid: 12632197
references.citation: Cardiovasc Res. 2003 Apr 1;58(1):89-98
references.pmid: 12667949
references.citation: Cardiovasc Res. 2008 Jan 15;77(2):245-55
references.pmid: 18006456
references.citation: Biochem Biophys Res Commun. 1985 Apr 16;128(1):449-56
references.pmid: 3985981
references.citation: Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H97-H104
references.pmid: 18441200
references.citation: Physiol Rev. 1991 Jul;71(3):849-908
references.pmid: 2057528
references.citation: Biophys J. 1984 May;45(5):913-25
references.pmid: 6733242
references.citation: Biochem Biophys Res Commun. 1988 Feb 29;151(1):441-9
references.pmid: 2450540
references.citation: Biophys J. 1993 Aug;65(2):865-81
references.pmid: 8218910
references.citation: Physiol Rev. 2002 Oct;82(4):893-922
references.pmid: 12270947
references.citation: Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2024-38
references.pmid: 17586620
references.citation: Ann N Y Acad Sci. 2005 Jun;1047:86-98
references.pmid: 16093487
references.citation: Clin Exp Pharmacol Physiol. 2006 Nov;33(11):1107-13
references.pmid: 17042923
references.citation: Biophys J. 2001 Apr;80(4):1915-25
references.pmid: 11259304
references.citation: Circulation. 1999 Mar 23;99(11):1499-507
references.pmid: 10086976
references.citation: Eur Heart J. 2001 Mar;22(5):356-63
references.pmid: 11207076
references.citation: Circ Res. 2003 Apr 4;92(6):668-75
references.pmid: 12600876
references.citation: J Muscle Res Cell Motil. 1999 Aug;20(5-6):555-67
references.pmid: 10555074
references.citation: Circ Res. 2006 Sep 29;99(7):740-8
references.pmid: 16946134
references.citation: J Gen Physiol. 2000 Dec;116(6):873-82
references.pmid: 11099353
references.citation: Biophys J. 1998 Dec;75(6):2801-10
references.pmid: 9826602
references.citation: J Gen Physiol. 1991 May;97(5):913-47
references.pmid: 1650812
references.citation: Circ Res. 2003 Jul 11;93(1):40-5
references.pmid: 12791706
references.citation: Science. 1993 May 7;260(5109):807-9
references.pmid: 8387229
references.citation: J Physiol. 2003 Jan 1;546(Pt 1):19-31
references.pmid: 12509476