Regulatory Mechanisms In Intestinal Motility

Summary

Principal Investigator: Kenton M Sanders
Abstract: DESCRIPTION OF OVERALL PROGRAM (provided by applicant) This Program Project seeks to understand basic cellular mechanisms responsible for gastrointestinal (Gl) motility. Knowledge of the basic structures and mechanisms of the neuromuscular apparatus of the Gl tract provides insights about how normal Gl motility is accomplished and why dysmotilities develop in the abnormal Gl tract. The long range benefit of this information will be to provide the basis for novel methods for treatment of abnormal Gl transit and to improve the quality of life for human patients. The neuromuscular apparatus of the Gl tract is extremely complex and function depends upon integrated activity of several types of cells. We have designed 4 projects that will explore various aspects of enteric neurotransmission, pacemaker activity, and smooth muscle function. Project 1, using a novel murine genetic model in which interstitial cells of Cajal (ICC) express a fluorescent protein, will seek to understand the mechanism of pacemaker activity and how pacemaker function is affected in diabetes and ICC hyperplasia. Project 3 will seek to understand regulation of smooth muscle excitability and how the activity of non-selective cation conductances contributes to normal and abnormal responses of muscle cells. Project 4 will investigate the release, function and metabolism of a novel neurotransmitter substance that is important for regulating colonic motor function. Project 5 will study the plasticity of ICC and how and why these cells are lost in type II diabetes. This project will also seek to develop techniques for restoring networks of ICC after damage. These primary investigations will be supported by 3 Core facilities designed to provide administration and informatics support and cutting-edge techniques, including cell and organotypic cultures, construction of transgenic animals, cytometry and fluorescence activated cell sorting, analysis of molecular expression, and a variety of morphological techniques. For the purpose of translating our findings from animal models to the function of the human Gl tract, many of our experiments will be conducted on tissues and cells of human patients that have been recovered from surgery for carcinomas. The investigative team is highly synergistic and collaborative, and the PPG has a long track-record of productivity and novel discovery
Funding Period: 1997-05-01 - 2015-04-30
more information: NIH RePORT

Top Publications

  1. pmc Expression and function of a T-type Ca2+ conductance in interstitial cells of Cajal of the murine small intestine
    Haifeng Zheng
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, Nevada and
    Am J Physiol Cell Physiol 306:C705-13. 2014
  2. pmc Anoctamins and gastrointestinal smooth muscle excitability
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, NV 89557, USA
    Exp Physiol 97:200-6. 2012
  3. pmc Electrical slow waves in the mouse oviduct are dependent upon a calcium activated chloride conductance encoded by Tmem16a
    Rose Ellen Dixon
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, 89557, USA
    Biol Reprod 86:1-7. 2012
  4. pmc Hydrodynamic delivery of human IL-15 cDNA increases murine natural killer cell recovery after syngeneic bone marrow transplantation
    Isabel Barao
    University of Nevada, Reno, Department of Microbiology and Immunology, Reno, Nevada, USA
    Biol Blood Marrow Transplant 17:1754-64. 2011
  5. pmc Electrical slow waves in the mouse oviduct are dependent on extracellular and intracellular calcium sources
    Rose Ellen Dixon
    Dept of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Am J Physiol Cell Physiol 301:C1458-69. 2011
  6. pmc Identification of histamine receptors and effects of histamine on murine and simian colonic excitability
    H Kim
    Department of Internal Medicine, School of Medicine, Gyeongsang National University, Jinju, Korea
    Neurogastroenterol Motil 23:949-e409. 2011
  7. pmc Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal
    Mei Hong Zhu
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 589:4565-82. 2011
  8. ncbi Cyclic ADP-ribose requires CD38 to regulate the release of ATP in visceral smooth muscle
    Leonie Durnin
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557 0575, USA
    FEBS J 278:3095-108. 2011
  9. pmc Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle
    Laura Dwyer
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, 89557, USA
    Am J Physiol Gastrointest Liver Physiol 301:G287-96. 2011
  10. pmc Serum response factor-dependent MicroRNAs regulate gastrointestinal smooth muscle cell phenotypes
    Chanjae Park
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA
    Gastroenterology 141:164-75. 2011

Research Grants

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
  2. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
  3. Ether Lipids, Elcosanoids, and Lung Cell Pathophysiology
    CHRISTINA CARROLL LESLIE; Fiscal Year: 2013
  4. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
  5. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
  6. DIABETES AND ENDOCRINOLOGY RESEARCH CENTER
    Domenico Accili; Fiscal Year: 2013
  7. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
  8. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
  9. Semi-volatile PCBs: Sources, Exposures, Toxicities
    Larry W Robertson; Fiscal Year: 2013
  10. Protein-glycan Interactions in the Vascular System
    Lijun Xia; Fiscal Year: 2013

Detail Information

Publications78

  1. pmc Expression and function of a T-type Ca2+ conductance in interstitial cells of Cajal of the murine small intestine
    Haifeng Zheng
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, Nevada and
    Am J Physiol Cell Physiol 306:C705-13. 2014
    ..With previous studies our data suggest that T-type current is required for entrainment of pacemaker activity within ICC and for active propagation of slow waves in ICC networks. ..
  2. pmc Anoctamins and gastrointestinal smooth muscle excitability
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, NV 89557, USA
    Exp Physiol 97:200-6. 2012
    ..Anoctamin 1 is a prominent conductance in ICC, and these channels appear to be involved in pacemaker activity and in responses to enteric excitatory neurotransmitters...
  3. pmc Electrical slow waves in the mouse oviduct are dependent upon a calcium activated chloride conductance encoded by Tmem16a
    Rose Ellen Dixon
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, 89557, USA
    Biol Reprod 86:1-7. 2012
    ..These data suggest that Tmem16a-encoded CaCCs contribute to membrane potential and are responsible for the upstroke and plateau phases of oviduct slow waves...
  4. pmc Hydrodynamic delivery of human IL-15 cDNA increases murine natural killer cell recovery after syngeneic bone marrow transplantation
    Isabel Barao
    University of Nevada, Reno, Department of Microbiology and Immunology, Reno, Nevada, USA
    Biol Blood Marrow Transplant 17:1754-64. 2011
    ..These results support the use of cytokine gene transfer-based regimens as a platform to augment NK cell recovery after BMT...
  5. pmc Electrical slow waves in the mouse oviduct are dependent on extracellular and intracellular calcium sources
    Rose Ellen Dixon
    Dept of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Am J Physiol Cell Physiol 301:C1458-69. 2011
    ..In conclusion, results from this study suggest that slow wave generation in the oviduct is voltage dependent, occurs in a membrane potential window, and is dependent on extracellular calcium and functional SERCA pumps...
  6. pmc Identification of histamine receptors and effects of histamine on murine and simian colonic excitability
    H Kim
    Department of Internal Medicine, School of Medicine, Gyeongsang National University, Jinju, Korea
    Neurogastroenterol Motil 23:949-e409. 2011
    ..The profiles of H receptor expression in animal models used to study inflammatory diseases are unknown...
  7. pmc Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal
    Mei Hong Zhu
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 589:4565-82. 2011
    ..These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation...
  8. ncbi Cyclic ADP-ribose requires CD38 to regulate the release of ATP in visceral smooth muscle
    Leonie Durnin
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557 0575, USA
    FEBS J 278:3095-108. 2011
    ....
  9. pmc Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle
    Laura Dwyer
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, 89557, USA
    Am J Physiol Gastrointest Liver Physiol 301:G287-96. 2011
    ..In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle...
  10. pmc Serum response factor-dependent MicroRNAs regulate gastrointestinal smooth muscle cell phenotypes
    Chanjae Park
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA
    Gastroenterology 141:164-75. 2011
    ..MicroRNAs (miRNA) regulate transitions among SMC phenotypes. The SMC miRNA transcriptome (SMC miRNAome) and its regulation by SRF have not been determined...
  11. pmc Relationship between interstitial cells of Cajal, fibroblast-like cells and inhibitory motor nerves in the internal anal sphincter
    Caroline A Cobine
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Cell Tissue Res 344:17-30. 2011
    ..Thus, a close morphological arrangement exists between inhibitory motor neurons, ICC-IM and PDGFRα(+)-IM suggesting that some functional interaction occurs between them contributing to inhibitory neurotransmission in the IAS...
  12. pmc Contribution of Rho-kinase to membrane excitability of murine colonic smooth muscle
    O Bayguinov
    Department of Physiology and Cell Biology, University of Nevada Reno, School of Medicine, USA
    Br J Pharmacol 163:638-48. 2011
    ..However, there is evidence that Rho-kinase also modulates other cellular effectors such as ion channels...
  13. pmc A functional role for the 'fibroblast-like cells' in gastrointestinal smooth muscles
    Masaaki Kurahashi
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 589:697-710. 2011
    ..We characterized these responses, and our results provide a new hypothesis about the role of fibroblast-like cells in smooth muscle tissues...
  14. pmc Neuroeffector apparatus in gastrointestinal smooth muscle organs
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 588:4621-39. 2010
    ..This review examines the evidence for and against the role of ICC in motor neurotransmission and outlines areas for additional investigation that would help further resolve this controversy...
  15. pmc β-nicotinamide adenine dinucleotide is an enteric inhibitory neurotransmitter in human and nonhuman primate colons
    Sung Jin Hwang
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557 0352, USA
    Gastroenterology 140:608-617.e6. 2011
    ..Here β-NAD and ATP were compared as possible inhibitory neurotransmitters in human and monkey colons...
  16. pmc Kitlow stem cells cause resistance to Kit/platelet-derived growth factor alpha inhibitors in murine gastrointestinal stromal tumors
    Michael R Bardsley
    Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota 55905, USA
    Gastroenterology 139:942-52. 2010
    ..In mouse models we investigated whether Kit(low) ICC progenitors could represent an inherently Kit/Pdgfra inhibitor-resistant reservoir for GIST...
  17. pmc Time-dependent disruption of oviduct pacemaker cells by Chlamydia infection in mice
    Rose Ellen Dixon
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    Biol Reprod 83:244-53. 2010
    ..muridarum infection. As the infection resolves, NOS2 expression decreases, ICC-OVI networks recover, and pacemaker activity resumes...
  18. pmc Interstitial cells of Cajal in the cynomolgus monkey rectoanal region and their relationship to sympathetic and nitrergic nerves
    C A Cobine
    Dept of Physiology and Cell Biology, Univ of Nevada School of Medicine, Reno, 89557, USA
    Am J Physiol Gastrointest Liver Physiol 298:G643-56. 2010
    ..Additionally, the presence of numerous minibundles, each containing both ICC-IAS and nerves, suggests that this muscle functions as a multiunit type muscle...
  19. pmc Analysis of pacemaker activity in the human stomach
    Poong Lyul Rhee
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 589:6105-18. 2011
    ..Our findings suggest that extracellular electrical recording has underestimated human slow wave frequency and mechanisms of human gastric function may differ from standard laboratory animal models...
  20. pmc Adenosine 5-diphosphate-ribose is a neural regulator in primate and murine large intestine along with β-NAD(+)
    Leonie Durnin
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557 0575, USA
    J Physiol 590:1921-41. 2012
    ..Taken together, our observations support a novel hypothesis in which multiple purines contribute to enteric inhibitory regulation of gastrointestinal motility...
  21. pmc P2Y1 purinoreceptors are fundamental to inhibitory motor control of murine colonic excitability and transit
    Sung Jin Hwang
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 590:1957-72. 2012
    ..These data demonstrate the importance of purinergic neurotransmission in regulating colonic motility and confirm pharmacological experiments suggesting that purinergic neurotransmission is mediated via P2Y1 receptors...
  22. ncbi Extensive projections of myenteric serotonergic neurons suggest they comprise the central processing unit in the colon
    T Okamoto
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
    Neurogastroenterol Motil 26:556-70. 2014
    ..5-Hydroxytryptamine (5-HT, serotonin) is an important regulator of colonic motility and secretion; yet the role of serotonergic neurons in the colon is controversial...
  23. pmc Distribution and Ca(2+) signalling of fibroblast-like (PDGFR(+)) cells in the murine gastric fundus
    Salah A Baker
    K M Sanders Department of Physiology and Cell Biology, University of Nevada School of Medicine, MS 352, Reno, NV 89557, USA
    J Physiol 591:6193-208. 2013
    ..Activation of Ca(2+) release is likely to be the signalling mechanism in PDGFRα(+) cells responsible for the transduction of purinergic enteric inhibitory input in gastric fundus muscles...
  24. pmc Important role of mucosal serotonin in colonic propulsion and peristaltic reflexes: in vitro analyses in mice lacking tryptophan hydroxylase 1
    Dante J Heredia
    T K Smith Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 591:5939-57. 2013
    ..Our observations suggest that mucosal 5-HT is essential for reflexes driven by mucosal stimulation and is also important for normal propagation of CMMCs and propulsion of pellets in the isolated colon...
  25. pmc Differential expression of genes related to purinergic signaling in smooth muscle cells, PDGFRα-positive cells, and interstitial cells of Cajal in the murine colon
    L E Peri
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
    Neurogastroenterol Motil 25:e609-20. 2013
    ..We compared gene transcripts for purinergic receptors and membrane-bound enzymes for purine degradation expressed by each cell type of the SIP syncytium...
  26. pmc Oxidative stress disrupts purinergic neuromuscular transmission in the inflamed colon
    Jane A Roberts
    Department of Neurological Sciences, University of Vermont, Burlington, VT 05405, USA
    J Physiol 591:3725-37. 2013
    ....
  27. pmc Establishment of pacemaker activity in tissues allotransplanted with interstitial cells of Cajal
    C J McCann
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Neurogastroenterol Motil 25:e418-28. 2013
    ..We sought to develop a model where ICC could be allotransplanted into intestines naturally devoid of these cells...
  28. pmc Ca2+ sensitization pathways accessed by cholinergic neurotransmission in the murine gastric fundus
    Bhupal P Bhetwal
    University of Nevada School of Medicine, Physiology and Cell Biology, University of Nevada, Reno, CMM203E, Reno, NV 89557, USA
    J Physiol 591:2971-86. 2013
    ..Furthermore, these findings demonstrate that bath application of contractile agonists to gastrointestinal smooth muscles does not mimic physiological responses to cholinergic neurotransmission...
  29. pmc A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon
    Masaaki Kurahashi
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Am J Physiol Gastrointest Liver Physiol 304:G823-34. 2013
    ..Subepithelial PDGFRα(+) cells occupy an important niche in the lamina propria and may function in transduction of sensory and immune signals and in the maintenance of mucosal homeostasis...
  30. pmc Functional role of vasoactive intestinal polypeptide in inhibitory motor innervation in the mouse internal anal sphincter
    K D Keef
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 591:1489-506. 2013
    ..In conclusion, this study identified an ultraslow component of inhibitory NMT in the IAS mediated by VIP. In vivo, this pathway may be activated with larger rectal distensions, leading to a more prolonged period of anal relaxation...
  31. pmc Differential release of β-NAD(+) and ATP upon activation of enteric motor neurons in primate and murine colons
    L Durnin
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557 0575, USA
    Neurogastroenterol Motil 25:e194-204. 2013
    ..The study was designed to clarify the sources of purines in colons of Cynomolgus monkeys and C57BL/6 mice...
  32. pmc Stretch-dependent sensitization of post-junctional neural effectors in colonic muscles
    K J Won
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
    Neurogastroenterol Motil 25:e101-13. 2013
    ..Input from enteric motor neurons regulates this motility. Here we examined stretch-dependent responses in circular muscle strips of murine colon...
  33. pmc Functional expression of SK channels in murine detrusor PDGFR+ cells
    Haeyeong Lee
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 591:503-13. 2013
    ....
  34. ncbi Regulation of gastrointestinal motility--insights from smooth muscle biology
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Anderson Medical Sciences, Reno, NV 89557, USA
    Nat Rev Gastroenterol Hepatol 9:633-45. 2012
    ..Here we provide an overview of the cells and mechanisms that generate smooth muscle contractile behaviour and gastrointestinal motility...
  35. pmc Neuronal and extraneuronal release of ATP and NAD(+) in smooth muscle
    Violeta N Mutafova-Yambolieva
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557 0575, USA
    IUBMB Life 64:817-24. 2012
    ....
  36. ncbi Interstitial cells in the primate gastrointestinal tract
    Peter J Blair
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, 89557, USA
    Cell Tissue Res 350:199-213. 2012
    ..Since similar sub-populations of ICC exist within the GI tract of primates and rodents and the use of rodents to study the functional roles of different classes of ICC is warranted...
  37. ncbi Relationship between enteric neurons and interstitial cells in the primate gastrointestinal tract
    P J Blair
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Neurogastroenterol Motil 24:e437-49. 2012
    ..The present study was performed to determine if enteric nerve fibers form close anatomical relationships with ICC and PDGFRα(+) cells throughout the primate GI tract...
  38. ncbi Ionic conductances regulating the excitability of colonic smooth muscles
    Sang Don Koh
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89558, USA
    Neurogastroenterol Motil 24:705-18. 2012
    ..Studies of isolated SIP cells have begun to unravel the mechanisms responsible for neural responses. This review discusses ion channels that set and regulate RMP of SIP cells and how neurotransmitters regulate membrane potential...
  39. pmc ICC-MY coordinate smooth muscle electrical and mechanical activity in the murine small intestine
    G W Hennig
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
    Neurogastroenterol Motil 22:e138-51. 2010
    ..Previous studies have documented loss of slow waves and aberrant motility in the small intestine of W/W(V) mice where myenteric ICC (ICC-MY) are significantly depleted...
  40. pmc Phospholipase C-independent effects of 3M3FBS in murine colon
    Laura Dwyer
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    Eur J Pharmacol 628:187-94. 2010
    ..In contrast, both compounds also caused an increase in [Ca(2+)](i) in an agonistic manner. Therefore caution must be employed when interpreting their effects at the tissue and cellular level...
  41. pmc Septal interstitial cells of Cajal conduct pacemaker activity to excite muscle bundles in human jejunum
    Hyun Tai Lee
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    Gastroenterology 133:907-17. 2007
    ..It is important to determine their functional significance, because a loss of ICC in humans is associated with disordered motility. Our aims were therefore to determine the role of ICC-SEP in activating the thick CM in the human jejunum...
  42. pmc Inactivation of inducible nitric oxide synthase protects intestinal pacemaker cells from postoperative damage
    Hiroe Yanagida
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 582:755-65. 2007
    ..Thus, management of iNOS expression or activity prior to intestinal surgery protects against postsurgical dysmotility and reduces the severity of postoperative ileus...
  43. ncbi The mechanism and spread of pacemaker activity through myenteric interstitial cells of Cajal in human small intestine
    Hyun Tai Lee
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89577, USA
    Gastroenterology 132:1852-65. 2007
    ..Our aims were to determine whether myenteric ICC (ICC-MY) in human jejunum are pacemaker cells and whether these cells actively propagate pacemaker activity...
  44. ncbi Immunocytochemical identification of interstitial cells of Cajal in the murine fundus using a live-labelling technique
    C J Stratton
    Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557, USA
    Neurogastroenterol Motil 19:152-9. 2007
    ..This method will prove useful to investigate the ultrastructural changes that occur in ICC networks in animal models of motility disorders that are associated with the loss of these cells...
  45. pmc Kit mutants and gastrointestinal physiology
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 578:33-42. 2007
    ..This review describes the use of genetic models to understand the important physiological role of ICC in the GI tract...
  46. ncbi Activation of neural circuitry and Ca2+ waves in longitudinal and circular muscle during CMMCs and the consequences of rectal aganglionosis in mice
    Nick J Spencer
    Dept of Physiology and Cell Biology, Univ of Nevada School of Medicine, Reno, NV 89557, USA
    Am J Physiol Gastrointest Liver Physiol 292:G546-55. 2007
    ..Aganglionosis results in a sporadic and sustained asynchrony in Ca(2+) wave firing between the LM and CM and an absence of CMMCs...
  47. pmc Interstitial cells of Cajal at the clinical and scientific interface
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 576:683-7. 2006
    ..Success in this endeavour might improve the quality of life for millions of patients...
  48. ncbi Selective labeling and isolation of functional classes of interstitial cells of Cajal of human and murine small intestine
    Hui Chen
    Department of Physiology and Cell Biology, School of Medicine, University of Nevada Reno, Reno, NV 89557, USA
    Am J Physiol Cell Physiol 292:C497-507. 2007
    ..ICC-DMP express neurotransmitter receptors and signaling intermediate molecules that are consistent with their role in neuromuscular neurotransmission...
  49. ncbi Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract
    Elizabeth A H Beckett
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    Dev Dyn 236:60-72. 2007
    ..ICC-MY demonstrate significant plasticity in gastrointestinal tissues. Manipulation of the ICC phenotype might provide useful therapies in gastrointestinal disease where the Kit-positive cell population is either lost or amplified...
  50. pmc Interstitial cells of Cajal: a new perspective on smooth muscle function
    Kenton M Sanders
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 576:721-6. 2006
    ..This perspectives article gives a short overview of the history of ICC research and directions for future investigation...
  51. ncbi Deglycosylation of the beta1-subunit of the BK channel changes its biophysical properties
    Brian M Hagen
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557 0046, USA
    Am J Physiol Cell Physiol 291:C750-6. 2006
    ..These data suggest that glycosylations on the beta1-subunit in smooth muscle cells can modify the biophysical properties of BK channels...
  52. ncbi Nucleotide regulation of the voltage-dependent nonselective cation conductance in murine colonic myocytes
    Kevin P Monaghan
    Dept of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Am J Physiol Cell Physiol 291:C985-94. 2006
    ..Our data suggest that ATP activates I(VNSCC) and depresses I(L) via binding of P2Y(4) receptors and stimulation of the phospholipase C/PKC pathway...
  53. ncbi Template switching within exons 3 and 4 of KV11.1 (HERG) gives rise to a 5' truncated cDNA
    S Ro
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, 89557, USA
    Biochem Biophys Res Commun 345:1342-9. 2006
    ..The 171 bp deletion was absent at the higher temperature. Our results suggest that the sequence and secondary structure of mRNA in the G/C rich region leads to template switching producing a cDNA product with a 171 bp deletion...
  54. pmc Effects of female steroid hormones on A-type K+ currents in murine colon
    Elizabeth A H Beckett
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, MS 352, Reno, NV 89557, USA
    J Physiol 573:453-68. 2006
    ..These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause...
  55. ncbi VIP and PACAP regulate localized Ca2+ transients via cAMP-dependent mechanism
    Brian M Hagen
    Dept of Physiology and Cell Biology, Univ of Nevada School of Medicine, Reno, NV 89557 0046, USA
    Am J Physiol Cell Physiol 291:C375-85. 2006
    ..Regulation of Ca2+ transients by VIP and PACAP occurs via adenylyl cyclase, increased synthesis of cAMP, and PKA-dependent regulation of ryanodine receptor channels...
  56. ncbi Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis
    Viktor J Horváth
    Department of Physiology and Cell Biology, University of Nevada, Reno, Nevada, USA
    Gastroenterology 130:759-70. 2006
    ..Most murine gastric ICC depend on stem cell factor (SCF) signaling but can also be maintained with insulin or insulin-like growth factor-I (IGF-I). We investigated whether SCF could mediate the actions of insulin and IGF-I...
  57. pmc Interstitial cells of Cajal in the deep muscular plexus mediate enteric motor neurotransmission in the mouse small intestine
    Sean M Ward
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 573:147-59. 2006
    ..Thus, ICC-DMP appear to serve a function in the small intestine that is similar to the role of the intramuscular ICC in the stomach...
  58. ncbi Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine
    Hui Chen
    Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, NV 89557, USA
    Physiol Genomics 31:492-509. 2007
    ..Our results may lead to the identification of novel biomarkers for ICC and provide directions for further studies designed to understand ICC function in health and disease...
  59. pmc Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle
    Violeta N Mutafova-Yambolieva
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Proc Natl Acad Sci U S A 104:16359-64. 2007
    ..beta-NAD meets the traditional criteria for a neurotransmitter that contributes to enteric inhibitory regulation of visceral smooth muscles...
  60. pmc Block of inhibitory junction potentials and TREK-1 channels in murine colon by Ca2+ store-active drugs
    Sung Jin Hwang
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 586:1169-84. 2008
    ..These effects appear to be due, in part, to the cAMP/PKA stimulatory actions of these drugs and inhibitory effects of TREK channels...
  61. ncbi A model to study the phenotypic changes of interstitial cells of Cajal in gastrointestinal diseases
    Seungil Ro
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    Gastroenterology 138:1068-78.e1-2. 2010
    ..Studies of ICC have been hampered by the low density of these cells and difficulties in recognizing these cells in cell dispersions...
  62. pmc CaM kinase II in colonic smooth muscle contributes to dysmotility in murine DSS-colitis
    S Qureshi
    Department of Physiology and Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, NV 89557, USA
    Neurogastroenterol Motil 22:186-95, e64. 2010
    ..The aim of this study was to investigate the mechanisms by which disrupted intracellular Ca(2+) signalling contributes to the impaired contractility of colon circular smooth muscles...
  63. pmc A Ca(2+)-activated Cl(-) conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity
    Mei Hong Zhu
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 587:4905-18. 2009
    ..These findings demonstrate a role for a Ca(2+)-activated Cl(-) conductance in slow wave current in ICC and are consistent with the idea that ANO1 participates in pacemaker activity...
  64. pmc Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles
    Sung Jin Hwang
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Physiol 587:4887-904. 2009
    ..Loss of function of ANO1 did not inhibit the development of ICC networks that appeared structurally normal as indicated by Kit antibodies. These data demonstrate the fundamental role of ANO1 in the generation of slow waves in GI ICC...
  65. pmc Caffeine inhibits nonselective cationic currents in interstitial cells of Cajal from the murine jejunum
    Nan Ge Jin
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    Am J Physiol Cell Physiol 297:C971-8. 2009
    ..STICs are responsible for unitary potentials in intact muscles, and the block of these events by caffeine is consistent with the idea that a nonselective cation conductance underlies unitary potentials in ICC...
  66. pmc Biophysically based mathematical modeling of interstitial cells of Cajal slow wave activity generated from a discrete unitary potential basis
    R A Faville
    University of Auckland, Auckland, New Zealand
    Biophys J 96:4834-52. 2009
    ..Moreover, numerical investigations show that our ICC model is capable of qualitatively replicating a wide range of experimental observations...
  67. pmc Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles
    Thomas A Jepps
    Division of Basic Medical Sciences, St George s, University of London, London, United Kingdom
    Am J Physiol Gastrointest Liver Physiol 297:G107-15. 2009
    ..Drugs that selectively block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility disorders such as constipation associated with irritable bowel syndrome...
  68. ncbi Heterogeneities in ICC Ca2+ activity within canine large intestine
    Hyun Tai Lee
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA
    Gastroenterology 136:2226-36. 2009
    ..We used Ca(2+) imaging to investigate whether interstitial cells of Cajal (ICCs) at these borders generated distinct rhythms...
  69. ncbi Interstitial cells of Cajal contain signalling molecules for transduction of nitrergic stimulation in guinea pig caecum
    S Iino
    Department of Morphological and Physiological Sciences, University of Fukui Faculty of Medical Sciences, Eiheiji, Fukui, Japan
    Neurogastroenterol Motil 21:542-50, e12-3. 2009
    ..These data show that ICC express the downstream signalling molecules necessary to transduce nitrergic signals and activate inhibitory pathways and thus are primary targets for NO released from neurons and other cells in the GI tract...
  70. pmc Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice
    K D McCloskey
    Physiology, Division of Basic Medical Sciences, Medical Biology Centre, 97 Lisburn Road, Belfast, Northern Ireland, UK
    Br J Pharmacol 156:273-83. 2009
    ....
  71. pmc Chlamydia infection causes loss of pacemaker cells and inhibits oocyte transport in the mouse oviduct
    Rose Ellen Dixon
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada
    Biol Reprod 80:665-73. 2009
    ..This, accompanied by retention of oviduct secretions, may contribute to the development of tubal factor infertility...
  72. ncbi Changes in the structure and function of ICC networks in ICC hyperplasia and gastrointestinal stromal tumors
    Joong Goo Kwon
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    Gastroenterology 136:630-9. 2009
    ....
  73. ncbi Regulation of SRF/CArG-dependent gene transcription during chronic partial obstruction of murine small intestine
    J Chen
    Department of Physiology and Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, NV 89557, USA
    Neurogastroenterol Motil 20:829-42. 2008
    ..These results suggest that changes in the expression and interactions between SRF, myocardin, Elk-1, and c-fos play key roles in the phenotypic switching of small intestine smooth muscles in response to mechanical obstruction...
  74. ncbi Regulation of smooth muscle excitation and contraction
    K M Sanders
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Neurogastroenterol Motil 20:39-53. 2008
    ....
  75. pmc Progenitors of interstitial cells of cajal in the postnatal murine stomach
    Andrea Lorincz
    Department of Physiology and Cell Biology, University of Nevada, Reno, USA
    Gastroenterology 134:1083-93. 2008
    ..Our goal was to identify ICC precursors in postnatal murine gastric muscles...
  76. pmc A biophysically based mathematical model of unitary potential activity in interstitial cells of Cajal
    R A Faville
    The Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
    Biophys J 95:88-104. 2008
    ..The model presented here provides a basis to quantitatively analyze UP depolarizations and the biophysical mechanisms underlying their production...
  77. ncbi An outwardly rectifying and deactivating chloride channel expressed by interstitial cells of cajal from the murine small intestine
    Sean P Parsons
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    J Membr Biol 221:123-32. 2008
    ..The permeability sequence of the channel was I(-)>>Br(-)>or=Cl(-)>Asp(-). It was unaffected in magnitude or rectification by changing the free Ca2+ concentration of the bath between <10 nM, 100 nM (control) and 2 mM ...
  78. ncbi Spatial and temporal mapping of pacemaker activity in interstitial cells of Cajal in mouse ileum in situ
    Kyu Joo Park
    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Am J Physiol Cell Physiol 290:C1411-27. 2006
    ..The activity of ICC-MY is driven by intracellular Ca(2+) handling mechanisms and entrained by voltage-dependent Ca(2+) entry and coupling of cells via gap junctions...

Research Grants30

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..
  2. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
    ..ular tone, in the pathophysiology of hypertension and cardiovascular disease. ..
  3. Ether Lipids, Elcosanoids, and Lung Cell Pathophysiology
    CHRISTINA CARROLL LESLIE; Fiscal Year: 2013
    ..By using multidisciplinary approaches, we will determine the structural identity of lipid mediators, the molecular mechanisms involved in their production and how they function to regulate lung responses. ..
  4. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  5. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
    ..These projects are supported by 3 Cores: Core A: The Administrative Core;Core B: The Physiology Core and Core C: The Imaging-Cell Culture Core. (End of Abstract) ..
  6. DIABETES AND ENDOCRINOLOGY RESEARCH CENTER
    Domenico Accili; Fiscal Year: 2013
    ....
  7. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..
  8. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
    ..A major objective of this Program Project is to inform decisions of the IPF Clinical Network by providing information that can be translated into novel therapeutic strategies for IPF. ..
  9. Semi-volatile PCBs: Sources, Exposures, Toxicities
    Larry W Robertson; Fiscal Year: 2013
    ..These data and dietary studies in the last Aim will provide a scientific basis for risk assessment and advice for stakeholders with the ultimate goal to protect highly-exposed individuals and populations. ..
  10. Protein-glycan Interactions in the Vascular System
    Lijun Xia; Fiscal Year: 2013
    ..This information may suggest new approaches to treat heart attacks, strokes, and other cardiovascular disorders. ..