Abstract
The urinary bladder has two functions: to store urine, when it is relaxed and highly compliant; and void its contents, when intravesical pressure rises due to co-ordinated contraction of detrusor smooth muscle in the bladder wall. Superimposed on this description are two observations: (1) the normal, relaxed bladder develops small transient increases of intravesical pressure, mirrored by local bladder wall movements; (2) pathological, larger pressure variations (detrusor overactivity) can occur that may cause involuntary urine loss and/or detrusor overactivity. Characterisation of these spontaneous contractions is important to understand: how normal bladder compliance is maintained during filling; and the pathophysiology of detrusor overactivity. Consideration of how spontaneous contractions originate should include the structural complexity of the bladder wall. Detrusor smooth muscle layer is overlain by a mucosa, itself a complex structure of urothelium and a lamina propria containing sensory nerves, micro-vasculature, interstitial cells and diffuse muscular elements.
Several theories, not mutually exclusive, have been advanced for the origin of spontaneous contractions. These include intrinsic rhythmicity of detrusor muscle; modulation by non-muscular pacemaking cells in the bladder wall; motor input to detrusor by autonomic nerves; regulation of detrusor muscle excitability and contractility by the adjacent mucosa and spontaneous contraction of elements of the lamina propria. This chapter will consider evidence for each theory in both normal and overactive bladder and how their significance may vary during ageing and development. Further understanding of these mechanisms may also identify novel drug targets to ameliorate the clinical consequences of large contractions associated with detrusor overactivity.
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References
Seth JH, Panicker JN, Fowler CJ. The neurological organization of micturition. Handb Clin Neurol. 2013;117:111–7.
Khandelwal P, Abraham SN, Apodaca G. Cell biology and physiology of the uroepithelium. Am J Physiol Ren Physiol. 2009;297:F1477–501.
Tanaka ST, Ishii K, DeMarco RT, Pope JC, Brock JW, Hayward SW. Endodermal origin of bladder trigone inferred from mesenchymal-epithelial interactions. J Urol. 2010;183:386–91.
Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A. The standardisation of terminology of lower urinary tract function. Neurourol Urodyn. 2002;21:167–78.
Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, Coyne K, Kelleher C, Hampel C, Artibani W, Abrams P. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50:1306–14.
Diamond P, Hassonah S, Alarab M, Lovatsis D, Drutz HP. The prevalence of detrusor overactivity amongst patients with symptoms of overactive bladder: a retrospective cohort study. Int Urogynecol J. 2012;23:1577–80.
Mosso A, Pellacani P. Sur les fonctions de la vessie. Arch Ital Biol 1882; 1: 97–128. Tr. R. Feneley 2011, Burleigh Press, Bristol, UK. ISBN 9780956941305.
van Os-Bossagh P, Kosterman LM, Hop WC, Westerhof BE, de Bakker JV, Drogendijk AC, van Duyl WA. Micromotions of bladder wall in chronic pelvic pain (CPP): a pilot study. Int Urogynecol J Pelvic Floor Dysfunct. 2001;12:89–96.
Drake MJ, Harvey IJ, Gillespie JI, van Duyl WA. Localized contractions in the normal human bladder and in urinary urgency. BJU Int. 2005;95:1002–5.
Drake MJ, Hedlund P, Harvey IJ, Pandita RK, Andersson KE, Gillespie JI. Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder. J Urol. 2003;170:276–9.
Kanai A, Roppolo J, Ikeda Y, Zabbarova I, Tai C, Birder L, Griffiths D, de Groat W, Fry CH. Origin of spontaneous activity in neonatal and adult rat bladders and its enhancement by stretch and muscarinic agonists. Am J Physiol Ren Physiol. 2007;292:F1065–72.
Parsons BA, Drake MJ, Gammie A, Fry CH, Vahabi B. The validation of a functional, isolated pig bladder model for physiological experimentation. Front Pharmacol. 2012;3:52.
Vahabi B, Drake MJ. Physiological and pathophysiological implications of micromotion activity in urinary bladder function. Acta Physiol. 2015;213:360–70.
Lagou M, Drake MJ, Gillespie JI. Volume-induced effects on the isolated bladder: a possible local reflex. BJU Int. 2004;94:1356–65.
Drake M, Gillespie J, Hedlund P, Harvey I, Lagou M, Andersson KE. Muscarinic stimulation of the rat isolated whole bladder: pathophysiological models of detrusor overactivity. Auton Autacoid Pharmacol. 2006;26:261–6.
Hammad FT, Stephen B, Lubbad L, Morrison JF, Lammers WJ. Macroscopic electrical propagation in the guinea pig urinary bladder. Am J Physiol Ren Physiol. 2014;307:F172–82.
Sibley GN. A comparison of spontaneous and nerve-mediated activity in bladder muscle from man, pig and rabbit. J Physiol. 1984;354:431–43.
Hashitani H, Brading AF, Suzuki H. Correlation between spontaneous electrical, calcium and mechanical activity in detrusor smooth muscle of the guinea-pig bladder. Br J Pharmacol. 2004;141:183–93.
Montgomery BS, Fry CH. The action potential and net membrane currents in isolated human detrusor smooth muscle cells. J Urol. 1992;147:176–84.
Nakahira Y, Hashitani H, Fukuta H, Sasaki S, Kohri K, Suzuki H. Effects of isoproterenol on spontaneous excitations in detrusor smooth muscle cells of the guinea pig. J Urol. 2001;166:335–40.
Meng E, Young JS, Brading AF. Spontaneous activity of mouse detrusor smooth muscle and the effects of the urothelium. Neurourol Urodyn. 2008;27:79–87.
Sui G, Fry CH, Malone-Lee J, Wu C. Aberrant Ca2+ oscillations in smooth muscle cells from overactive human bladders. Cell Calcium. 2009;45:456–64.
Fry CH, Young JS, Jabr RI, McCarthy C, Ikeda Y, Kanai AJ. Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists. Am J Physiol Ren Physiol. 2012;302:F1447–54.
Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, Ford AP, Burnstock G. P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci. 2001;21:5670–7.
McCarthy CJ, Zabbarova IV, Brumovsky PR, Roppolo JR, Gebhart GF, Kanai AJ. Spontaneous contractions evoke afferent nerve firing in mouse bladders with detrusor overactivity. J Urol. 2009;181:1459–66.
Heppner TJ, Tykocki NR, Hill-Eubanks D, Nelson MT. Transient contractions of urinary bladder smooth muscle are drivers of afferent nerve activity during filling. J Gen Physiol. 2016;147:323–35.
Drake MJ, Kanai A, Bijos DA, Ikeda Y, Zabbarova I, Vahabi B, Fry CH. The potential role of unregulated autonomous bladder micromotions in urinary storage and voiding dysfunction; overactive bladder and detrusor underactivity. BJU Int. 2017;119:22–9.
Abrams P. Describing bladder storage function: overactive bladder syndrome and detrusor overactivity. Urology. 2003;62:28–37.
Kinder RB, Mundy AR. Pathophysiology of idiopathic detrusor instability and detrusor hyper-reflexia. An in vitro study of human detrusor muscle. Br J Urol. 1987;60:509–15.
Kato K, Wein AJ, Radzinski C, Longhurst PA, McGuire EJ, Miller LF, Elbadawi A, Levin RM. Short term functional effects of bladder outlet obstruction in the cat. J Urol. 1990;143:1020–5.
Fry CH. Physiological properties of the lower urinary tract. In: Mundy AR, Fitpatrick JM, Neal DE, George NJ, editors. The scientific basis of urology. Colchester: Informa Healthcare; 2010. p. 244–65.
Fry CH, Chess-Williams R, Hashitani H, Kanai AJ, McCloskey K, Takeda M, Vahabi B. Cell biology. In: Abrams P, Cardozo L, Wagg A, Wein A, editors. Incontinence. 6th ed. Paris: ICUD ICS; 2016. p. 148–258. ISBN: 978-0-9569607-3-3.
Sui GP, Wu C, Fry CH. A description of Ca2+ channels in human detrusor smooth muscle. BJU Int. 2003;92:476–82.
Anderson UA, Carson C, Johnston L, Joshi S, Gurney AM, McCloskey KD. Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity. Br J Pharmacol. 2013;169:1290–304.
Petkov GV. Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology. Am J Phys Regul Integr Comp Phys. 2014;307:R571–84.
Fry CH, Bayliss M, Young JS, Hussain M. Influence of age and bladder dysfunction on the contractile properties of isolated human detrusor smooth muscle. BJU Int. 2011;108:E91–6.
Harvey RA, Skennerton DE, Newgreen D, Fry CH. The contractile potency of adenosine triphosphate and ecto-adenosine triphosphatase activity in guinea pig detrusor and detrusor from patients with a stable, unstable or obstructed bladder. J Urol. 2002;168:1235–9.
Hashitani H, Yanai Y, Suzuki H. Role of interstitial cells and gap junctions in the transmission of spontaneous Ca2+ signals in detrusor smooth muscles of the guinea-pig urinary bladder. J Physiol. 2004;559:567–81.
Gray SM, McGeown JG, McMurray G, McCloskey KD. Functional innervation of Guinea-pig bladder interstitial cells of cajal subtypes: neurogenic stimulation evokes in situ calcium transients. PLoS One. 2013;8:e53423.
Hirst GD, Edwards FR. Electrical events underlying organized myogenic contractions of the guinea pig stomach. J Physiol. 2006;576:659–65.
Sanders KM, Ward SM, Koh SD. Interstitial cells: regulators of smooth muscle function. Physiol Rev. 2014;94:859–907.
Hashitani H. Interaction between interstitial cells and smooth muscles in the lower urinary tract and penis. J Physiol. 2006;576:707–14.
Koh BH, Roy R, Hollywood MA, Thornbury KD, McHale NG, Sergeant GP, Hatton WJ, Ward SM, Sanders KM, Koh SD. Platelet-derived growth factor receptor-α cells in mouse urinary bladder: a new class of interstitial cells. J Cell Mol Med. 2012;16:691–700.
Monaghan KP, Johnston L, McCloskey KD. Identification of PDGFRα positive populations of interstitial cells in human and guinea pig bladders. J Urol. 2012;188:639–47.
Lee H, Koh BH, Yamasaki E, George NE, Sanders KM, Koh SD. UTP activates small-conductance Ca2+-activated K+ channels in murine detrusor PDGFRα+ cells. Am J Physiol Ren Physiol. 2015;309:F569–74.
Akino H, Chapple CR, McKay N, Cross RL, Murakami S, Yokoyama O, Chess-Williams R, Sellers DJ. Spontaneous contractions of the pig urinary bladder: the effect of ATP-sensitive potassium channels and the role of the mucosa. BJU Int. 2008;102:1168–74.
Moro C, Uchiyama J, Chess-Williams R. Urothelial/lamina propria spontaneous activity and the role of M3 muscarinic receptors in mediating rate responses to stretch and carbachol. Urology. 2011;78:1442.e9–15.
Kushida N, Fry CH. On the origin of spontaneous activity in the bladder. BJU Int. 2016;117:982–92.
Ikeda Y, Kanai A. Urotheliogenic modulation of intrinsic activity in spinal cord-transected rat bladders: role of mucosal muscarinic receptors. Am J Physiol Ren Physiol. 2008;295:F454–61.
Xin W, Li N, Cheng Q, Petkov GV. BK channel-mediated relaxation of urinary bladder smooth muscle: a novel paradigm for phosphodiesterase type 4 regulation of bladder function. J Pharmacol Exp Ther. 2014;349:56–65.
Ikeda Y, Fry C, Hayashi F, Stolz D, Griffiths D, Kanai A. Role of gap junctions in spontaneous activity of the rat bladder. Am J Physiol Ren Physiol. 2007;293:F1018–25.
Roosen A, Datta SN, Chowdhury RA, Patel PM, Kalsi V, Elneil S, Dasgupta P, Kessler TM, Khan S, Panicker J, Fry CH, Brandner S, Fowler CJ, Apostolidis A. Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment. Eur Urol. 2009;55:1440–8.
Moro C, Leeds C, Chess-Williams R. Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide. Eur J Pharmacol. 2012;674:445–9.
McDonnell BM, Buchanan PJ, Prise KM, McCloskey KD. Acute radiation impacts contractility of guinea-pig bladder strips affecting mucosal-detrusor interactions. PLoS One. 2018;13:e0193923.
Moro C, Tajouri L, Chess-Williams R. Adrenoceptor function and expression in bladder urothelium and lamina propria. Urology. 2013;81:211.e1–7.
Sadananda P, Chess-Williams R, Burcher E. Contractile properties of the pig bladder mucosa in response to neurokinin A: a role for myofibroblasts? Br J Pharmacol. 2008;153:1465–73.
Hinz B. Masters and servants of the force: the role of matrix adhesions in myofibroblast force perception and transmission. Eur J Cell Biol. 2006;85:175–81.
Lee K, Isogai A, Antoh M, Kajioka S, Eto M, Hashitani H. Role of K+ channels in regulating spontaneous activity in the muscularis mucosae of guinea pig bladder. Eur J Pharmacol. 2018;818:30–7.
Heppner TJ, Layne JJ, Pearson JM, Sarkissian H, Nelson MT. Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder. Am J Phys Regul Integr Comp Phys. 2011;301:R351–62.
Isogai A, Lee K, Mitsui R, Hashitani H. Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder. Pflugers Arch. 2016;468:1573–85.
Hashitani H, Mitsui R, Shimizu Y, Higashi R, Nakamura K. Functional and morphological properties of pericytes in suburothelial venules of the mouse bladder. Br J Pharmacol. 2012;167:1723–36.
Hashitani H, Lang RJ. Spontaneous activity in the microvasculature of visceral organs: role of pericytes and voltage-dependent Ca2+ channels. J Physiol. 2016;594:555–65.
Wiseman OJ, Fowler CJ, Landon DN. The role of the human bladder lamina propria myofibroblast. BJU Int. 2003;91:89–93.
Wu C, Sui GP, Fry CH. Purinergic regulation of guinea pig suburothelial myofibroblasts. J Physiol. 2004;559:231–43.
Sui GP, Rothery S, Dupont E, Fry CH, Severs NJ. Gap junctions and connexin expression in human suburothelial interstitial cells. BJU Int. 2002;90:118–29.
Drake MJ, Fry CH, Eyden B. Structural characterization of myofibroblasts in the bladder. BJU Int. 2006;97:29–32.
Sharif-Afshar AR, Donohoe JM, Pope JC 4th, Adams MC, Brock JW 3rd, Bhowmick NA. Stromal hyperplasia in male bladders upon loss of transforming growth factor-beta signaling in fibroblasts. J Urol. 2005;174:1704–7.
Birder L, Andersson KE. Urothelial signaling. Physiol Rev. 2013;93:653–80.
Okinami T, Imamura M, Nishikawa N, Negoro H, Sugino Y, Yoshimura K, Kanematsu A, Hashitani H, Ogawa O. Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis. PLoS One. 2014;9:e104216.
Palani D, Ghildyal P, Manchanda R. Effects of heptanol and carbenoxolone on noradrenaline induced contractions in guinea pig vas deferens. Auton Neurosci. 2007;137:56–62.
Heppner TJ, Hennig GW, Nelson MT, Vizzard MA. Rhythmic calcium events in the lamina propria network of the urinary bladder of rat pups. Front Syst Neurosci. 2017;11:87.
Hawthorn MH, Chapple CR, Cock M, Chess-Williams R. Urothelium-derived inhibitory factor(s) influences on detrusor muscle contractility in vitro. Br J Pharmacol. 2000;129:416–9.
Sui GP, Wu C, Severs N, Newgreen D, Fry CH. The association between T-type Ca2+ current and outward current in isolated human detrusor cells from stable and overactive bladders. BJU Int. 2007;99:436–41.
Sui GP, Coppen SR, Dupont E, Rothery S, Gillespie J, Newgreen D, Severs NJ, Fry CH. Impedance measurements and connexin expression in human detrusor muscle from stable and unstable bladders. BJU Int. 2003;92:297–305.
Fry CH, Gammie A, Drake MJ, Abrams P, Kitney DG, Vahabi B. Estimation of bladder contractility from intravesical pressure-volume measurements. Neurourol Urodyn. 2017;36:1009–14.
Oger S, Behr-Roussel D, Gorny D, Bernabé J, Comperat E, Chartier-Kastler E, Denys P, Giuliano F. Effects of potassium channel modulators on myogenic spontaneous phasic contractile activity in human detrusor from neurogenic patients. BJU Int. 2011;108:604–11.
Hristov KL, Afeli SA, Parajuli SP, Cheng Q, Rovner ES, Petkov GV. Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca2+-activated K+ channels. PLoS One. 2013;8:e68052.
Mills IW, Greenland JE, McMurray G, McCoy R, Ho KM, Noble JG, Brading AF. Studies of the pathophysiology of idiopathic detrusor instability: the physiological properties of the detrusor smooth muscle and its pattern of innervation. J Urol. 2000;163:646–51.
Soder RP, Petkov GV. Large conductance Ca2+-activated K+ channel activation with NS1619 decreases myogenic and neurogenic contractions of rat detrusor smooth muscle. Eur J Pharmacol. 2011;670:252–9.
Hristov KL, Parajuli SP, Soder RP, Cheng Q, Rovner ES, Petkov GV. Suppression of human detrusor smooth muscle excitability and contractility via pharmacological activation of large conductance Ca2+-activated K+ channels. Am J Phys Cell Physiol. 2012;302:C1632–41.
Parajuli SP, Hristov KL, Soder RP, Kellett WF, Petkov GV. NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels. Br J Pharmacol. 2013;168:1611–25.
Soder RP, Parajuli SP, Hristov KL, Rovner ES, Petkov GV. SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle. Am J Phys Regul Integr Comp Phys. 2013;304:R155–63.
Young JS, Meng E, Cunnane TC, Brain KL. Spontaneous purinergic neurotransmission in the mouse urinary bladder. J Physiol. 2008;586:5743–55.
Südhof TC. α-Latrotoxin and its receptors: neurexins and CIRL/latrophilins. Annu Rev Neurosci. 2001;24:933–62.
Gevaert T, Vanstreels E, Daelemans D, Franken J, van der Aa T, Roskams T, de Ridder D. Identification of different phenotypes of interstitial cells in the upper and deep lamina propria of the human bladder dome. J Urol. 2014;192:1555–63.
Sui GP, Wu C, Fry CH. Characterization of the purinergic receptor subtype on guinea-pig suburothelial myofibroblasts. BJU Int. 2006;97:1327–31.
Birder LA, Barrick SR, Roppolo JR, Kanai AJ, de Groat WC, Kiss S, Buffington CA. Feline interstitial cystitis results in mechanical hypersensitivity and altered ATP release from bladder urothelium. Am J Physiol Ren Physiol. 2003;285:F423–9.
Sun Y, Chai TC. Augmented extracellular ATP signaling in bladder urothelial cells from patients with interstitial cystitis. Am J Phys Cell Physiol. 2006;290:C27–34.
Munoz A, Smith CP, Boone TB, Somogyi GT. Overactive and underactive bladder dysfunction is reflected by alterations in urothelial ATP and NO release. Neurochem Int. 2011;58:295–300.
Munoz A, Somogyi GT, Boone TB, Ford AP, Smith CP. Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3 receptors. BJU Int. 2012;110:E409–14.
Shiina K, Hayashida KI, Ishikawa K, Kawatani M. ATP release from bladder urothelium and serosa in a rat model of partial bladder outlet obstruction. Biomed Res. 2016;37:299–304.
McLatchie LM, Young JS, Fry CH. Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations. Br J Pharmacol. 2014;171:3394–403.
Kullmann FA, Artim DE, Birder LA, de Groat WC. Activation of muscarinic receptors in rat bladder sensory pathways alters reflex bladder activity. J Neurosci. 2008;28:1977–87.
McLatchie LM, Fry CH. ATP release from freshly isolated guinea-pig bladder urothelial cells: a quantification and study of the mechanisms involved. BJU Int. 2015;115:987–93.
Birder LA, Ruan H, Chopra B, Xiang Z, Barrick S, Buffington CA, Roppolo JR, Ford AP, de Groat WC, Burnstock G. Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis. Am J Phys. 2004;287:F1084–91.
Beckel JM, Kanai A, Lee SJ, de Groat WC, Birder LA. Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells. Am J Phys. 2006;290:F103–10.
Chess-Williams R. Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional. Auton Autacoid Pharmacol. 2002;22:1330–145.
Birder LA, Nealen M, Kiss S, de Groat WC, Caterina MJ, Wang E, Apodaca G, Kanai AJ. Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells. J Neurosci. 2002;22:8063–70.
Birder LA, Kanai A, de Groat WC, Kiss S, Nealen ML, Burke NE, Dineley KE, Watkins S, Reynolds IJ, Caterina MJ. Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci. 2001;98:13396–401.
Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M, Patel AS, Nelson JB, Futrell WJ, Yoshimura N, Chancellor MB, De Miguel F. Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol. 2004;172:1175–8.
Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Högestätt ED, Zygmunt PM. Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol. 2008;53:391–9.
Miyamoto T, Mochizuki T, Nakagomi H, Kira S, Watanabe M, Takayama Y, Suzuki Y, Koizumi S, Takeda M, Tominaga M. Functional role for piezo1 in stretch-evoked Ca2+ influx and ATP release in urothelial cell cultures. J Biol Chem. 2014;289:16565–75.
Roosen A, Wu C, Sui G, Chowdhury RA, Patel PM, Fry CH. Characteristics of spontaneous activity in the bladder trigone. Eur Urol. 2009;56:346–53.
Callahan SM, Creed KE. Electrical and mechanical activity of the isolated lower urinary tract of the guinea-pig. Br J Pharmacol. 1981;74:353–8.
Kelley RS, Vardy MD, Simons GR, Chen H, Ascher-Walsh C, Brodman M. A pilot study of cardiac electrophysiology catheters to map and pace bladder electrical activity. Neurourol Urodyn. 2017;36:1174–7.
Shafik A. Role of the trigone in micturition. J Endourol. 1998;12:273–7.
Lentle RG, Reynolds GW, Janssen PW, Hulls CM, King QM, Chambers JP. Characterisation of the contractile dynamics of the resting ex vivo urinary bladder of the pig. BJU Int. 2015;116:973–83.
Roosen A, Fry CH, Sui G, Wu C. Adreno-muscarinic synergy in the bladder trigone: calcium-dependent and -independent mechanisms. Cell Calcium. 2009;45:11–7.
Wuest M, Witte LP, Michel-Reher MB, Propping S, Braeter M, Strugala GJ, Wirth MP, Michel MC, Ravens U. The muscarinic receptor antagonist propiverine exhibits α1-adreno-ceptor antagonism in human prostate and porcine trigone. World J Urol. 2011;29:149–55.
Oh SJ, Lee KH, Kim SJ, Kim KW, Kim KM, Choi H. Active properties of the urinary bladder: in vitro comparative studies between adult and neonatal rats. BJU Int. 2000;85:1126–33.
Szigeti GP, Somogyi GT, Csernoch L, Széll EA. Age-dependence of the spontaneous activity of the rat urinary bladder. J Muscle Res Cell Motil. 2005;26:23–9.
Vahabi B, Sellers DJ, Bijos DA, Drake MJ. Phasic contractions in urinary bladder from juvenile versus adult pigs. PLoS One. 2013;8(3):e58611.
Sugaya K, De Groat WC. Micturition reflexes in the in vitro neonatal rat brain stem-spinal cord-bladder preparation. Am J Phys Regul Integr Comp Phys. 1994;266:R658–67.
Ng YK, de Groat WC, Wu HY. Muscarinic regulation of neonatal rat bladder spontaneous contractions. Am J Phys Regul Integr Comp Phys. 2006;291:R1049–59.
Ekman M, Andersson KE, Arner A. Receptor-induced phasic activity of newborn mouse bladders is inhibited by protein kinase C and involves T-type Ca2+ channels. BJU Int. 2009;104:690–7.
Lluel P, Palea S, Barras M, Grandadam F, Heudes D, Bruneval P, Corman B, Martin DJ. Functional and morphological modifications of the urinary bladder in aging female rats. Am J Phys Regul Integr Comp Phys. 2000;278:R964–72.
Daly DM, Nocchi L, Liaskos M, McKay NG, Chapple C, Grundy D. Age-related changes in afferent pathways and urothelial function in the male mouse bladder. J Physiol. 2014;592:537–49.
Yoshida M, Miyamae K, Iwashita H, Otani M, Inadome A. Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology. 2004;63(3 Suppl):17–23.
Sui G, Fry CH, Montgomery B, Roberts M, Wu R, Wu C. Purinergic and muscarinic modulation of ATP release from the urothelium and its paracrine actions. Am J Physiol Ren Physiol. 2014;306:F286–98.
Yoshida M, Masunaga K, Satoji Y, Maeda Y, Nagata T, Inadome A. Basic and clinical aspects of non-neuronal acetylcholine: expression of non-neuronal acetylcholine in urothelium and its clinical significance. J Pharmacol Sci. 2008;106:193–8.
Yu Y, de Groat WC. Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder-pelvic nerve preparation by purinergic agonists and cyclophosphamide pretreatment. Am J Physiol Ren Physiol. 2008;294:F1146–56.
Chun AL, Wallace LJ, Gerald MC, Levin RM, Wein AJ. Effect of age on in vivo urinary bladder function in the rat. J Urol. 1988;139:625–7.
Smith PP, DeAngelis A, Kuchel GA. Detrusor expulsive strength is preserved, but responsiveness to bladder filling and urinary sensitivity is diminished in the aging mouse. Am J Phys Regul Integr Comp Phys. 2012;302:R577–86.
Hotta H, Morrison JF, Sato A, Uchida S. The effects of aging on the rat bladder and its innervation. Jpn J Physiol. 1995;45:823–36.
Smith PP, DeAngelis A, Simon R. Evidence of increased centrally enhanced bladder compliance with ageing in a mouse model. BJU Int. 2015;115(2):322–9.
Zhao W, Aboushwareb T, Turner C, Mathis C, Bennett C, Sonntag WE, Andersson KE, Christ G. Impaired bladder function in aging male rats. J Urol. 2010;184:378–85.
Gorbunova V, Bozzella MJ, Seluanov A. Rodents for comparative aging studies: from mice to beavers. Age (Dordr). 2008;30:111–9.
Chen B, Zhang H, Liu L, Wang J, Ye Z. PK2/PKR1 signaling regulates bladder function and sensation in rats with cyclophosphamide-induced cystitis. Mediat Inflamm. 2015;2015:289519.
Brock N, Stekar J, Pohl J, Niemeyer U, Scheffler G. Acrolein, the causative factor of urotoxic side-effects of cyclophosphamide, ifosfamide, trofosfamide and sufosfamide. Arzneimittelforschung. 1979;29:659–61.
Haldar S, Dru C, Bhowmick NA. Mechanisms of hemorrhagic cystitis. Am J Clin Exp Urol. 2014;2:199–208.
Birder LA, de Groat W, Mills I, Morrison J, Thor K, Drake M. Neural control of the lower urinary tract: peripheral and spinal mechanisms. Neurourol Urodyn. 2010;29:128–39.
Sugaya K, Nishijima S, Tasaki S, Kadekawa K, Miyazato M, Ogawa Y. Effects of propiverine and naftopidil on the urinary ATP level and bladder activity after bladder stimulation in rats. Neurosci Lett. 2007;429:142–6.
Girard BM, Wolf-Johnston A, Braas KM, Birder LA, May V, Vizzard MA. PACAP-mediated ATP release from rat urothelium and regulation of PACAP/VIP and receptor mRNA in micturition pathways after cyclophosphamide (CYP)-induced cystitis. J Mol Neurosci. 2008;36:310–20.
Ikeda Y, Zabbarova IV, Birder LA, Wipf P, Getchell SE, Tyagi P, Fry CH, Drake MJ, Kanai AJ. Relaxin-2 therapy reverses radiation-induced fibrosis and restores bladder function in mice. Neurourol Urodyn. 2018;37:2441–51. https://doi.org/10.1002/nau.23721.
Chapple CR, Osman NI, Birder LA, van Koeveringe GA, Oelke M, Nitti VW, Drake MJ, Yamaguchi O, Abrams P, Smith PP. The underactive bladder: a new clinical concept? Eur Urol. 2015;68:351–3.
Gammie A, Kaper M, Dorrepaal C, Kos T, Abrams P. Signs and symptoms of detrusor underactivity: an analysis of clinical presentation and urodynamic tests from a large group of patients undergoing pressure flow studies. Eur Urol. 2016;69:361–9.
Kanai A, Fry C, Ikeda Y, Kullmann FA, Parsons B, Birder L. Implications for bidirectional signaling between afferent nerves and urothelial cells. Neurourol Urodyn. 2016;35:273–7.
Johnston L, Cunningham RM, Young JS, Fry CH, McMurray G, Eccles R, McCloskey KD. Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury. J Cell Mol Med. 2012;16:1533–43.
Chen J, Drzewiecki BA, Merryman WD, Pope JC. Murine bladder wall biomechanics following partial bladder obstruction. J Biomech. 2013;46:2752–5.
Griffiths D, Tadic SD. Bladder control, urgency, and urge incontinence: evidence from functional brain imaging. Neurourol Urodyn. 2008;27:466–74.
Bramich NJ, Brading AF. Electrical properties of smooth muscle in the guinea-pig urinary bladder. J Physiol. 1996;492:185–98.
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Fry, C.H., McCloskey, K.D. (2019). Spontaneous Activity and the Urinary Bladder. In: Hashitani, H., Lang, R. (eds) Smooth Muscle Spontaneous Activity. Advances in Experimental Medicine and Biology, vol 1124. Springer, Singapore. https://doi.org/10.1007/978-981-13-5895-1_5
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