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01-04-2014 | Review

Urinary tract pacemaker cells: current knowledge and insights from nonrenal pacemaker cells provide a basis for future discovery

Authors: Meghan M. Feeney, Norman D. Rosenblum

Published in: Pediatric Nephrology | Issue 4/2014

Abstract

Coordinated ureteric peristalsis propels urine from the kidney to the bladder. Cells in the renal pelvis and ureter spontaneously generate and propagate electrical activity to control this process. Recently, c-kit tyrosine kinase and hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) were identified in the upper urinary tract. Both of these proteins are required for coordinated proximal to distal contractions in the ureter. Alterations in pacemaker cell expression are present in multiple congenital kidney diseases, suggesting a functional contribution by these cells to pathologic states. In contrast to gut and heart pacemaker cells, the developmental biology of ureteric pacemaker cells, including cell lineage and signaling mechanisms, is undefined. Here, we review pacemaker cell identify and function in the urinary pelvis and ureter and the control of pacemaker function by Hedgehog-GLI signaling. Next, we highlight current knowledge of gut and heart pacemaker cells that is likely to provide insight into developmental mechanisms that could control urinary pacemaker cells.

David SG, Cebrian C, Vaughan ED Jr, Herzlinger D (2005) C-Kit and ureteral peristalsis. J Urol 173(1):292–295PubMedCrossRef

Hurtado R, Bub G, Herzlinger D (2009) The pelvis-kidney junction contains HCN3, a hyperpolarization-activated cation channel that triggers ureter peristalsis. Kidney Int 77(6):500–508PubMedCrossRef

Bozler E (1942) The activity of the pacemaker previous to the discharge of a muscular impulse. Am J Physiol 136:543–552

Gosling JA, Dixon JS (1971) Morphologic evidence that the renal calyx and pelvis control ureteric activity in the rabbit. Am J Anat 130:393–408PubMedCrossRef

Björk L, Nylén O (1972) Cineradiographic investigations of contraction in the normal upper urinary tract in man. Acta Radiol Diagn 12(1):25–33

Gosling JA (1970) Atypical muscle cells in the wall of the renal calix and pelvis with a note on their possible significance. Experientia 26(7):769–770PubMedCrossRef

Gosling JA, Dixon JS (1974) Species variation in the location of upper urinary tract pacemaker cells. Invest Urol 11(5):418–423PubMed

Klemm MF, Exintaris B, Lang RJ (1999) Identification of the cells underlying pacemaker activity in the guinea-pig upper urinary tract. J Physiol 519(Pt 3):867–884PubMedCrossRef

Metzger R, Schuster T, Till H, Stehr M, Franke F-E, Dietz H-G (2004) Cajal-like cells in the human upper urinary tract. J Urol 172(2):769–772PubMedCrossRef

10.

Metzger R, Schuster T, Till H, Franke F-E, Dietz H-G (2005) Cajal-like cells in the upper urinary tract: comparative study in various species. Pediatr Surg Intl 21(3):169–174CrossRef

11.

Pezzone MA, Watkins SC, Alber SM, King WE, de Groat WC, Chancellor MB, Fraser MO (2003) Identification of c-kit-positive cells in the mouse ureter: the interstitial cells of Cajal of the urinary tract. Am J Renal Physiol 284(5):F925–F929

12.

Lang RJ, Zoltkowski BZ, Hammer JM, Meeker WF, Wendt I (2007) Electrical characterization of interstitial cells of Cajal-like cells and smooth muscle cells isolated from the mouse ureteropelvic junction. J Urol 177(4):1573–1580PubMedCrossRef

13.

Tekgül S, Riedmiller H, Hoebeke P, Kočvara R, Nijman RJM, Radmayr C, Stein R, Dogan HS (2012) EAU guidelines on vesicoureteral reflux in children. Eur Urol 62(3):534–542PubMedCrossRef

14.

Schwentner C, Oswald J, Lunacek A, Fritsch H, Deibl M, Bartsch G, Radmayr C (2005) Loss of interstitial cells of Cajal and Gap junction protein connexin 43 at the vesicoureteral junction in children with vesicoureteral reflux. J Urol 174(5):1981–1986PubMedCrossRef

15.

Oberritter Z, Rolle U, Juhasz Z, Cserni T, Puri P (2009) Altered expression of c-kit-positive cells in the ureterovesical junction after surgically created vesicoureteral reflux. Pediatr Surg Int 25(12):1103–1107PubMedCrossRef

16.

Solari V, Piotrowska AP, Puri P (2003) Altered expression of interstitial cells of Cajal in congenital ureteropelvic junction obstruction. J Urol 170(6):2420–2422PubMedCrossRef

17.

Cain JE, Islam E, Haxho F, Blake J, Rosenblum ND (2011) GLI3 repressor controls functional development of the mouse ureter. J Clin Invest 121(3):1199–1206PubMedCentralPubMedCrossRef

18.

Christoffels VM, Smits GJ, Kispert A, Moorman AFM (2010) Development of the pacemaker tissues of the heart. Circ Res 106(2):240–254PubMedCrossRef

19.

Mangoni ME, Nargeot J (2007) Genesis and regulation of the heart automaticity. Physiol Rev 88(3):919–982CrossRef

20.

Mikawa T, Hurtado R (2007) Development of the cardiac conduction system. Semin Cell Dev Biol 18(1):90–100PubMedCrossRef

21.

Hoogaars WHM, Tessari A, Moorman AFM, de Boer PAJ, Hagoort J, Soufan AT, Campione M, Cristoffels VM (2004) The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Cardiovasc Res 62(3):489–499PubMedCrossRef

22.

Garcia-Frigola C, Shi Y, Evans SM (2003) Expression of the hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 during mouse heart development. Gene Expr Patterns 3(6):777–783PubMedCrossRef

23.

Buckingham M, Meilhac S, Zaffran S (2005) Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet 6(11):826–835PubMedCrossRef

24.

Christoffels VM, Mommersteeg MT, Trowe MO, Prall OW, de Gier-de Vries C, Soufan AT, Bussen M, Schuster-Gossler K, Harvey RP, Moorman AF, Kispert A (2006) Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circ Res 98(12):1555–1563PubMedCrossRef

25.

Mommersteeg MTM, Dominguez JN, Wiese C, Norden J, de Gier-de Vries C, Burch JB, Kispert A, Brown NA, Moorman AF, Christoffels VM (2010) The sinus venosus progenitors separate and diversify from the first and second heart fields early in development. Cardiovasc Res 87(1):92–101PubMedCrossRef

26.

Hoogaars WMH, Engel A, Brons JF, Verkerk AO, de Lange FJ, Wong LY, Bakker ML, Clout DE, Wakker V, Barnett P, Ravesloot JH, Moorman AF, Verheijck EE, Christoffels VM (2007) Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev 21(9):1098–1112PubMedCrossRef

27.

Mommersteeg MTM, Hoogaars WMH, Prall OWJ, de Gier-de Vries C, Wiese C, Clout DEW, Papaioannou VE, Brown NA, Harvey RP, Moorman AFM, Cristoffels VM (2007) Molecular pathway for the localized formation of the sinoatrial node. Circ Res 100(3):354–362PubMedCrossRef

28.

Blaschke RJ, Hahuij ND, Kuijper S, Just S, Wisse LJ, Deissler K, Maxelon T, Anastassiadis K, Spitzer J, Hardt SE, Scholer H, Feitma H, Rottbauer W, Blum M, Meijlink, Rappold G, Gittenberger-de Groot AC (2007) Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development. Circulation 115(14):1830–1838PubMedCrossRef

29.

Espinoza-Lewis RA, Yu L, He F, Liu H, Tang R, Shi J, Sun X, Martin JF, Wang D, Yang J, Chen Y (2009) Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5. Dev Biol 327(2):376–385PubMedCentralPubMedCrossRef

30.

Wiese C, Grieskamp T, Airik R, Mommersteeg MTM, Gardiwal A, de Gier-de Vries C, Schuster-Gossler K, Moorman AF, Kispert A, Christoffels VM (2009) Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circ Res 104(3):388–397PubMedCrossRef

31.

Cheng G, Litchenberg WH, Cole CJ, Mikawa T, Thompson RP, Gourdie RG (1999) Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineage. Development 126(22):5041–5049PubMed

32.

Aanhaanen WTJ, Brons JF, Domínguez JN, Rana MS, Norden J, Airik R, Wakker V, de Gier-de Vries C, Brown NA, Kispert A, Moorman AFM, Cristoffels VM (2009) The Tbx2+ primary myocardium of the atrioventricular canal forms the atrioventricular node and the base of the left ventricle. Circ Res 104(11):1267–1274PubMedCrossRef

33.

Streutker CJ, Huizinga JD, Driman DK, Riddell RH (2007) Interstitial cells of Cajal in health and disease. Part I: normal ICC structure and function with associated motility disorders. Histopathology 50(2):176–189PubMedCrossRef

34.

Torihashi S, Ward SM, Sanders KM (1997) Development of c-Kit-positive cells and the onset of electrical rhythmicity in murine small intestine. Gastroenterology 112(1):144–155PubMedCrossRef

35.

Lecoin L, Gabella G, Le Douarin N (1996) Origin of the c-kit-positive interstitial cells in the avian bowel. Development 122(3):725–733PubMed

36.

Young HM, Ciampoli D, Southwell BR, Newgreen DF (1996) Origin of interstitial cells of Cajal in the mouse intestine. Dev Biol 180(1):97–107PubMedCrossRef

37.

Kluppel M, Huizinga JD, Malysz J, Bernstein A (1998) Developmental origin and Kit-dependent development of the interstitial cells of Cajal in the mammalian small intestine. Dev Dyn 211(1):60–71PubMedCrossRef

38.

Sohal GS, Ali MM, Farooqui FA (2002) A second source of precursor cells for the developing enteric nervous system and interstitial cells of Cajal. Int J Dev Neurosci 20:619–626PubMedCrossRef

39.

Jiang J, Hui C-C (2008) Hedgehog signaling in development and cancer. Dev Cell 15(6):801–812PubMedCrossRef

Title: Urinary tract pacemaker cells: current knowledge and insights from nonrenal pacemaker cells provide a basis for future discovery
Authors: Meghan M. Feeney
Norman D. Rosenblum
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 4/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-013-2631-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Urinary tract pacemaker cells: current knowledge and insights from nonrenal pacemaker cells provide a basis for future discovery

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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