title: Modeling of the modulation by buffers of Ca2+ release through clusters of IP3 receptors.
abstract: Intracellular Ca(2+) release is a versatile second messenger system. It is modeled here by reaction-diffusion equations for the free Ca(2+) and Ca(2+) buffers, with spatially discrete clusters of stochastic IP(3) receptor channels (IP(3)Rs) controlling the release of Ca(2+) from the endoplasmic reticulum. IP(3)Rs are activated by a small rise of the cytosolic Ca(2+) concentration and inhibited by large concentrations. Buffering of cytosolic Ca(2+) shapes global Ca(2+) transients. Here we use a model to investigate the effect of buffers with slow and fast reaction rates on single release spikes. We find that, depending on their diffusion coefficient, fast buffers can either decouple clusters or delay inhibition. Slow buffers have little effect on Ca(2+) release, but affect the time course of the signals from the fluorescent Ca(2+) indicator mainly by competing for Ca(2+). At low [IP(3)], fast buffers suppress fluorescence signals, slow buffers increase the contrast between bulk signals and signals at open clusters, and large concentrations of buffers, either fast or slow, decouple clusters.
authors.affiliation: Institute for Theoretical Physics, Technische Universität Berlin, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zeller
authors.forename: S
authors.initials: S
authors.lastname: Rüdiger
authors.forename: H
authors.initials: H
authors.lastname: Engel
authors.forename: J
authors.initials: J
authors.lastname: Sneyd
authors.forename: G
authors.initials: G
authors.lastname: Warnecke
authors.forename: I
authors.initials: I
authors.lastname: Parker
authors.forename: M
authors.initials: M
authors.lastname: Falcke
mesh_terms: D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D003198:Computer Simulation; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D008954:Models, Biological
chemical_list: D002021:Buffers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D002118:Calcium
references.citation: J Biol Chem. 1990 Jun 15;265(17):9583-6
references.pmid: 2161835
references.citation: Cell Calcium. 1996 Aug;20(2):105-21
references.pmid: 8889202
references.citation: J Biol Chem. 1996 Aug 16;271(33):19817-25
references.pmid: 8702690
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6404-9
references.pmid: 19332787
references.citation: Biophys J. 2004 May;86(5):2660-73
references.pmid: 15111387
references.citation: J Physiol. 2003 Dec 15;553(Pt 3):775-88
references.pmid: 14555715
references.citation: J Biol Chem. 1989 Oct 15;264(29):17131-41
references.pmid: 2793847
references.citation: Biophys J. 1998 May;74(5):2722-30
references.pmid: 9591696
references.citation: J Physiol. 2001 Aug 15;535(Pt 1):3-16
references.pmid: 11507154
references.citation: Nat Rev Mol Cell Biol. 2000 Oct;1(1):11-21
references.pmid: 11413485
references.citation: EMBO Rep. 2007 Nov;8(11):1044-51
references.pmid: 17932510
references.citation: Science. 1991 Apr 5;252(5002):123-6
references.pmid: 2011747
references.citation: J Neurochem. 2007 Feb;100(3):727-35
references.pmid: 17263794
references.citation: Nature. 1991 Jun 27;351(6329):751-4
references.pmid: 1648178
references.citation: Genome Inform. 2007;18:44-53
references.pmid: 18546473
references.citation: Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9895-9
references.pmid: 1329108
references.citation: Biophys J. 2007 Oct 15;93(8):2597-608
references.pmid: 17586567
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2003 Sep;68(3 Pt 1):031914
references.pmid: 14524810
references.citation: Biophys J. 1997 Feb;72(2 Pt 1):674-90
references.pmid: 9017195
references.citation: EMBO J. 2001 Jan 15;20(1-2):65-76
references.pmid: 11226156
references.citation: J Physiol. 1999 Oct 1;520 Pt 1:187-201
references.pmid: 10517811
references.citation: J Biol Chem. 1998 Oct 16;273(42):27130-6
references.pmid: 9765231
references.citation: Biophys J. 1994 Jul;67(1):447-56
references.pmid: 7919018
references.citation: Curr Biol. 1999 Oct 7;9(19):1115-8
references.pmid: 10531009
references.citation: Biophys J. 2008 Mar 15;94(6):2404-11
references.pmid: 18065468
references.citation: Cell Calcium. 2002 Nov-Dec;32(5-6):321-34
references.pmid: 12543092
references.citation: Cell Calcium. 2008 Mar;43(3):285-95
references.pmid: 17698190
references.citation: Biophys J. 2003 Jan;84(1):28-41
references.pmid: 12524263
references.citation: FEBS Lett. 1986 Dec 1;209(1):1-8
references.pmid: 3803567
references.citation: J Neurosci. 1991 Jun;11(6):1496-507
references.pmid: 1675264
references.citation: Cell Calcium. 2008 Apr;43(4):367-74
references.pmid: 17716727
references.citation: Biophys J. 2003 Jan;84(1):42-56
references.pmid: 12524264
references.citation: Cell Calcium. 2009 Jan;45(1):65-76
references.pmid: 18639334
references.citation: EMBO J. 1999 Oct 1;18(19):5285-99
references.pmid: 10508162
references.citation: Nature. 2009 Apr 2;458(7238):655-9
references.pmid: 19348050
references.citation: J Physiol. 2004 Apr 15;556(Pt 2):447-61
references.pmid: 14755000
references.citation: Biophys J. 2003 Apr;84(4):2599-608
references.pmid: 12668468
references.citation: Neurosci Lett. 2006 Jan 2;391(3):102-7
references.pmid: 16198054
references.citation: Cell Calcium. 2007 Apr;41(4):365-78
references.pmid: 16962659