Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild‐type and <i>W/W<sup>v</sup></i> mice

McCloskey, Karen; Anderson, Ursula A.; Davidson, Ross; Bayguinov, Yulia; Sanders, Kenton M.; Ward, Sean M.

doi:10.1111/j.1476-5381.2008.00006.x

Cited by 46 publications

(46 citation statements)

References 45 publications

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“…ICCs have been identified in both the mucosae and detrusor, although their function is still unclear (47,71). Indeed, we observed Ca 2ϩ signals in structures linking muscle bundles in the mucosae (see Fig.…”

Section: R359mentioning

confidence: 75%

Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder

Heppner¹,

Layne²,

Pearson³

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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The muscularis mucosae, a type of smooth muscle located between the urothelium and the urinary bladder detrusor, has been described, although its properties and role in bladder function have not been characterized. Here, using mucosal tissue strips isolated from guinea pig urinary bladders, we identified spontaneous phasic contractions (SPCs) that appear to originate in the muscularis mucosae. This smooth muscle layer exhibited Ca 2ϩ waves and flashes, but localized Ca 2ϩ events (Ca 2ϩ sparks, purinergic receptor-mediated transients) were not detected. Ca 2ϩ flashes, often in bursts, occurred with a frequency (ϳ5.7/min) similar to that of SPCs (ϳ4/min), suggesting that SPCs are triggered by bursts of Ca 2ϩ flashes. The force generated by a single mucosal SPC represented the maximal force of the strip, whereas a single detrusor SPC was ϳ3% of maximal force of the detrusor strip. Electrical field stimulation (0.5-50 Hz) evoked force transients in isolated detrusor and mucosal strips. Inhibition of cholinergic receptors significantly decreased force in detrusor and mucosal strips (at higher frequencies). Concurrent inhibition of purinergic and cholinergic receptors nearly abolished evoked responses in detrusor and mucosae. Mucosal SPCs were unaffected by blocking smallconductance Ca 2ϩ -activated K ϩ (SK) channels with apamin and were unchanged by blocking large-conductance Ca 2ϩ -activated K ϩ (BK) channels with iberiotoxin (IbTX), indicating that SK and BK channels play a much smaller role in regulating muscularis mucosae SPCs than they do in regulating detrusor SPCs. Consistent with this, BK channel current density in myocytes from muscularis mucosae was ϳ20% of that in detrusor myocytes. These findings indicate that the muscularis mucosae in guinea pig represents a second smooth muscle compartment that is physiologically and pharmacologically distinct from the detrusor and may contribute to the overall contractile properties of the urinary bladder. calcium imaging; large-conductance calcium-activated potassium channel; potassium channels; calcium flashes; spontaneous phasic contractions THE URINARY BLADDER is a hollow, muscular organ that serves two functions: urine storage and elimination. The bladder wall is composed of detrusor smooth muscle, which accounts for a large fraction of the bladder mass, and a layer of transitional epithelial cells known as the urothelium, which lines the luminal surface of the urinary bladder. The detrusor smooth muscle has been extensively characterized and is clearly responsible for the majority of the contractile properties of the urinary bladder (1, 69). The urothelium, which was originally thought to simply act as a passive, impermeable barrier that prevents the movement of solutes from the urine into the bloodstream, is now recognized to possess a broad range of sensory and signal transduction functions that greatly influence bladder physiology (for a review, see Ref. 5).The detrusor exhibits two primary modes of contractile behavior: nerve-evoked contractions and spontaneo...

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Section: R359mentioning

confidence: 75%

Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder

Heppner¹,

Layne²,

Pearson³

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…9, B and C). It is well known that atropine and L-NAME inhibit the action of excitatory cholinergic and inhibitory nitrergic neurons, respectively (27,30). Therefore, it would be possible that the relatively increased response to atropine and L-NAME in the aged rats could reflect the degeneration of cholinergic and nitrergic neurons, respectively.…”

Section: Discussionmentioning

confidence: 99%

Fat deposition in the tunica muscularis and decrease of interstitial cells of Cajal and nNOS-positive neuronal cells in the aged rat colon

Jo¹,

Kim

Nam³

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Little is known about the time course of aging on interstitial cells of Cajal (ICC) of colon. The aim of this study was to investigate the change of morphology, ICC, and neuronal nitric oxide synthase (nNOS)-immunoreactive cells in the aged rat. The proximal colon of 344 Fischer rats at four different ages (6, 31, 74 wk, and 2 yr) were studied. The immunoreactivity of c-Kit, nNOS, anti-protein gene product 9.5, and synaptophysin were counted after immunohistochemistry. The c-kit, stem cell factor (ligand of Kit), and nNOS mRNA were measured by real-time PCR. c-Kit and nNOS protein were assessed by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The area of intramuscular fat deposition significantly increased with age after 31 wk. c-Kit-immunoreactive ICC and nNOS-immunoreactive neurons and nerve fibers significantly declined with age. mRNA and protein expression of c-kit and nNOS decreased with aging. The functional study showed that the spontaneous contractility was decreased in aged rat, whereas EFS responses in the presence of atropine and L-NG-Nitroarginine methyl ester were increased in aged rat. In conclusion, the decrease of proportion of proper smooth muscle, the density of ICC and nNOSimmunoreactive neuronal fibers, and the number of nNOS-immunoreactive neurons during the aging process may explain the agingassociated colonic dysmotility.aging; colon; interstitial cells of Cajal; neuronal nitric oxide synthase; rats; inbred F344 AGING LEADS TO THE IMPAIRMENT of organ function as a result of accumulation of diverse deleterious changes throughout the cells and tissues (16). Constipation is a common problem in the elderly and known to be associated with multiple factors, such as decreased intestinal secretory epithelial function, abnormal colonic motility caused by enteric neurodegeneration, and reduced contractile response of smooth muscle cells with age (3-5).Enteric neurodegeneration involves the loss of enteric neuron, especially excitatory cholinergic neurons (2). In contrast, nitrergic myenteric neurons are known to be selectively spared in the aged (9, 36, 45). However, there was a contrary report that nitrergic neurons decreased in aged rats (43). Nitrergic enteric neurons, which release nitric oxide (NO) generated by catalysis of neuronal NO synthase (nNOS), act as nonadrenergic, noncholinergic inhibitory neuron and induce colonic smooth muscle relaxation (42). This NO is known to enhance transit of the rat colon by mediating descending relaxation, which in turn facilitates propulsion of the colonic contents (32). Nitrergic nerves of colon may be an important component of colonic motility.Interstitial cells of Cajal (ICC) also play important roles in gastrointestinal motility. ICC play as an electrical pacemaker and mediate both inhibitory and excitatory motor neurotransmissions, which manifest as electrical slow waves in smooth muscles. Consequently, ICC contribute to segmenting and peristaltic contractile activity (20,33). ICC have ...

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“…In patients with diabetes, decreased BICCs were observed and this was suggested to contribute to incontinence (74). Alterations to BICC function have also been reported in OAB and obstructed bladder in both humans and animal models (79,92,(94)(95)(96)(97). Increased expression of connexin 43 has been reported in patients with OAB, suggesting increased signal transduction between BICCs and BSM cells, potentially leading to motility problems (98,99).…”

Section: Bladder Icc: An Old Cell Newly Implicated In Lower Urinary Tmentioning

confidence: 99%

Control of Urinary Drainage and Voiding

Hill

2015

Clinical Journal of the American Society of Nephrology

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Urine differs greatly in ion and solute composition from plasma and contains harmful and noxious substances that must be stored for hours and then eliminated when it is socially convenient to do so. The urinary tract that handles this output is composed of a series of pressurizable muscular compartments separated by sphincteric structures. With neural input, these structures coordinate the delivery, collection, and, ultimately, expulsion of urine. Despite large osmotic and chemical gradients in this waste fluid, the bladder maintains a highly impermeable surface in the face of a physically demanding biomechanical environment, which mandates recurring cycles of surface area expansion and increased wall tension during filling, followed by rapid wall compression during voiding. Afferent neuronal inflow from mucosa and submucosa communicates sensory information about bladder fullness, and voiding is initiated consciously through coordinated central and spinal efferent outflow to the detrusor, trigonal internal sphincter, and external urethral sphincter after periods of relative quiescence. Provocative new findings suggest that in some cases, lower urinary tract symptoms, such as incontinence, urgency, frequency, overactivity, and pain may be viewed as a consequence of urothelial defects (either urothelial barrier breakdown or inappropriate signaling from urothelial cells to underlying sensory afferents and potentially interstitial cells). This review describes the physiologic and anatomic mechanisms by which urine is moved from the kidney to the bladder, stored, and then released. Relevant clinical examples of urinary tract dysfunction are also discussed.

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Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild‐type and W/W^v mice

Abstract: Background and purpose: W/Wv and wild-type murine bladders were studied to determine whether the W/W v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Cited by 46 publications

References 45 publications

Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder

Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder

Fat deposition in the tunica muscularis and decrease of interstitial cells of Cajal and nNOS-positive neuronal cells in the aged rat colon

Control of Urinary Drainage and Voiding

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Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild‐type and W/Wv mice

Abstract: Background and purpose: W/Wv and wild-type murine bladders were studied to determine whether the W/W v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Cited by 46 publications

References 45 publications

Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder

Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder

Fat deposition in the tunica muscularis and decrease of interstitial cells of Cajal and nNOS-positive neuronal cells in the aged rat colon

Control of Urinary Drainage and Voiding

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Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild‐type and W/W^v mice