title: Spontaneous Ca(2+) transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine.
abstract: Interstitial cells of Cajal at the level of the deep muscular plexus (ICC-DMP) in the small intestine generate spontaneous Ca(2+) transients that consist of localized Ca(2+) events and limited propagating Ca(2+) waves. Ca(2+) transients in ICC-DMP display variable characteristics: from discrete, highly localized Ca(2+) transients to regionalized Ca(2+) waves with variable rates of occurrence, amplitude, duration and spatial spread. Ca(2+) transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells. Ca(2+) transients in ICC-DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s). Functional intracellular Ca(2+) stores are essential for spontaneous Ca(2+) transients, and the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump is necessary for maintenance of spontaneity. Ca(2+) release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3 Rs). Release from these channels is interdependent. ICC express transcripts of multiple RyRs and InsP3 Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression.
  
  
  
  Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC-DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC-DMP are mediated by activation of Ca(2+) -activated Cl(-) channels; thus, Ca(2+) signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca(2+) transients in ICC-DMP within intact jejunal muscles expressing a genetically encoded Ca(2+) indicator (GCaMP3) selectively in ICC. ICC-DMP displayed spontaneous Ca(2+) transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca(2+) transients was highly variable, and it was determined that firing was stochastic in nature. Ca(2+) transients were tabulated in multiple cells within fields of view, and no correlation was found between the events in adjacent cells. TTX (1 μm) significantly increased the occurrence of Ca(2+) transients, suggesting that ICC-DMP contributes to the tonic inhibition conveyed by ongoing activity of inhibitory motor neurons. Ca(2+) transients were minimally affected after 12 min in Ca(2+) free solution, indicating these events do not depend immediately upon Ca(2+) influx. However, inhibitors of sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump and blockers of inositol triphosphate receptor (InsP3 R) and ryanodine receptor (RyR) channels blocked ICC Ca(2+) transients. These data suggest an interdependence between RyR and InsP3 R in the generation of Ca(2+) transients. Itpr1 and Ryr2 were the dominant transcripts expressed by ICC. These findings provide the first high-resolution recording of the subcellular Ca(2+) dynamics that control the behaviour of ICC-DMP in situ.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: Salah A
authors.initials: SA
authors.lastname: Baker
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: Bernard T
authors.initials: BT
authors.lastname: Drumm
authors.affiliation: II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der TU München, München, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Hennig
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Ward
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D056885:Interstitial Cells of Cajal / Q000502:physiology*; D007421:Intestine, Small / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009197:Myenteric Plexus / Q000502:physiology*
chemical_list: D002118:Calcium
references.citation: Gastroenterology. 1995 May;108(5):1371-8
references.pmid: 7729628
references.citation: Nat Commun. 2014;5:3326
references.pmid: 24561718
references.citation: Eur J Biochem. 2002 Aug;269(15):3678-87
references.pmid: 12153564
references.citation: J Biol Chem. 2004 May 14;279(20):21287-93
references.pmid: 14985349
references.citation: J Neurosci. 2001 Aug 15;21(16):5944-51
references.pmid: 11487617
references.citation: Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1370-81
references.pmid: 19372102
references.citation: Cell Calcium. 2000 Feb;27(2):97-106
references.pmid: 10756976
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):12008-13
references.pmid: 8876253
references.citation: FASEB J. 2002 Aug;16(10 ):1145-50
references.pmid: 12153982
references.citation: Gastroenterology. 2009 Jun;136(7):2226-36
references.pmid: 19268670
references.citation: J Physiol. 2003 Feb 1;546(Pt 3):751-63
references.pmid: 12563001
references.citation: Science. 1995 Oct 27;270(5236):633-7
references.pmid: 7570021
references.citation: Am J Physiol Cell Physiol. 2007 Jan;292(1):C497-507
references.pmid: 16943245
references.citation: J Auton Nerv Syst. 1998 May 28;70(1-2):10-4
references.pmid: 9686898
references.citation: J Physiol. 2004 Apr 15;556(Pt 2):521-30
references.pmid: 14754997
references.citation: J Physiol. 1999 Jan 15;514 ( Pt 2):515-31
references.pmid: 9852332
references.citation: J Pharmacol Sci. 2003 May;92(1):35-42
references.pmid: 12832853
references.citation: J Physiol. 1994 Oct 1;480 ( Pt 1):91-7
references.pmid: 7853230
references.citation: Physiol Rev. 2014 Jul;94(3):859-907
references.pmid: 24987007
references.citation: Am J Physiol Cell Physiol. 2000 Feb;278(2):C235-56
references.pmid: 10666018
references.citation: J Physiol. 2004 Apr 15;556(Pt 2):585-99
references.pmid: 14754999
references.citation: Anat Rec. 2001 Jan 1;262(1):125-35
references.pmid: 11146435
references.citation: J Physiol. 2006 Jul 1;574(Pt 1):167-81
references.pmid: 16644801
references.citation: Biochemistry. 1989 Feb 21;28(4):1686-91
references.pmid: 2541762
references.citation: Neurogastroenterol Motil. 2013 Sep;25(9):e609-20
references.pmid: 23809506
references.citation: J Physiol. 2011 Sep 15;589(Pt 18):4565-82
references.pmid: 21768263
references.citation: Gut. 2000 Dec;47 Suppl 4:iv40-3; discussion iv52
references.pmid: 11076909
references.citation: Am J Physiol Cell Physiol. 2006 May;290(5):C1411-27
references.pmid: 16381798
references.citation: J Physiol. 2002 Sep 15;543(Pt 3):871-87
references.pmid: 12231645
references.citation: Gastroenterology. 2010 Mar;138(3):1068-78.e1-2
references.pmid: 19917283
references.citation: J Physiol. 1999 Jul 1;518(Pt 1):257-69
references.pmid: 10373707
references.citation: J Physiol. 2009 Oct 15;587(Pt 20):4905-18
references.pmid: 19703958
references.citation: J Physiol. 2006 Nov 1;576(Pt 3):675-82
references.pmid: 16973700
references.citation: Cell Tissue Res. 1995 May;280(2):201-10
references.pmid: 7781020
references.citation: Nat Methods. 2009 Dec;6(12):875-81
references.pmid: 19898485
references.citation: Am J Physiol. 1972 Jan;222(1):118-25
references.pmid: 4334054
references.citation: J Physiol. 2007 Sep 1;583(Pt 2):505-19
references.pmid: 17615099
references.citation: Cell Calcium. 2003 Sep;34(3):211-29
references.pmid: 12887969
references.citation: Circ Res. 2014 May 9;114(10):1623-39
references.pmid: 24812351
references.citation: Nature. 1995 Jan 26;373(6512):347-9
references.pmid: 7530333
references.citation: J Cell Biol. 1995 Mar;128(5):893-904
references.pmid: 7876312
references.citation: Neurogastroenterol Motil. 2003 Oct;15(5):531-43
references.pmid: 14507353
references.citation: Neurogastroenterol Motil. 2014 Sep;26(9):1298-310
references.pmid: 25039457
references.citation: J Comp Neurol. 2005 Dec 12;493(2):193-206
references.pmid: 16255030
references.citation: J Biol Chem. 1989 Oct 5;264(28):16776-85
references.pmid: 2550460
references.citation: J Biol Chem. 1987 Mar 5;262(7):3065-73
references.pmid: 2434495
references.citation: Am J Physiol Gastrointest Liver Physiol. 2011 Nov;301(5):G835-45
references.pmid: 21836058
references.citation: J Physiol. 2013 Dec 15;591(24):6193-208
references.pmid: 24144881
references.citation: Biochem Biophys Res Commun. 2005 Mar 11;328(2):640-6
references.pmid: 15694396
references.citation: J Cell Sci. 2004 Jun 1;117(Pt 13):2813-25
references.pmid: 15169838
references.citation: Arch Histol Jpn. 1977 Jun;40(3):171-201
references.pmid: 921492
references.citation: J Physiol. 2005 Dec 1;569(Pt 2):533-44
references.pmid: 16195318
references.citation: J Physiol. 2009 Oct 15;587(Pt 20):4887-904
references.pmid: 19687122
references.citation: Am J Physiol. 1984 Mar;246(3 Pt 1):G305-15
references.pmid: 6703058
references.citation: Proc Natl Acad Sci U S A. 1989 Sep;86(18):7280-4
references.pmid: 2550938
references.citation: Cell Tissue Res. 1993 Nov;274(2):249-56
references.pmid: 8269476
references.citation: Am J Physiol Cell Physiol. 2015 Sep 15;309(6):C403-14
references.pmid: 26135802
references.citation: J Physiol. 1994 Jun 15;477 ( Pt 3):459-68
references.pmid: 7932234
references.citation: Nat Commun. 2013;4:1630
references.pmid: 23535651
references.citation: J Physiol. 2015 Aug 1;593(15):3333-50
references.pmid: 26046824
references.citation: J Physiol. 2000 Apr 1;524 Pt 1:245-65
references.pmid: 10747196
references.citation: J Neurosci. 2000 Feb 15;20(4):1393-403
references.pmid: 10662830
references.citation: Front Mol Neurosci. 2014 Nov 18;7:88
references.pmid: 25477779
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9627-32
references.pmid: 18621682
references.citation: Neurogastroenterol Motil. 2004 Apr;16 Suppl 1:112-7
references.pmid: 15066015
references.citation: J Neurogastroenterol Motil. 2014 Apr 30;20(2):171-84
references.pmid: 24840370
references.citation: Cell Tissue Res. 2012 Nov;350(2):199-213
references.pmid: 22864981
references.citation: Cell Calcium. 2003 Jul;34(1):97-108
references.pmid: 12767897
references.citation: J Physiol. 2013 Jun 15;591(12 ):2971-86
references.pmid: 23613531
references.citation: Am J Physiol Gastrointest Liver Physiol. 2015 Feb 15;308(4):G287-97
references.pmid: 25501550
references.citation: Am J Physiol Cell Physiol. 2015 Apr 15;308(8):C608-20
references.pmid: 25631870
references.citation: Semin Cell Dev Biol. 2001 Feb;12(1):3-10
references.pmid: 11162741
references.citation: Am J Physiol Cell Physiol. 2011 Dec;301(6):C1458-69
references.pmid: 21881003
references.citation: J Physiol. 2015 Apr 15;593(8):1945-63
references.pmid: 25627983
references.citation: J Physiol. 1999 Aug 15;519 Pt 1:235-50
references.pmid: 10432354
references.citation: Physiol Genomics. 2007 Nov 14;31(3):492-509
references.pmid: 17895395
references.citation: Arch Histol Cytol. 1999 Oct;62(4):295-316
references.pmid: 10596941
references.citation: J Physiol. 1998 Dec 15;513 ( Pt 3):711-8
references.pmid: 9824712