Ca2+ regulation in detrusor smooth muscle from developing fetal sheep bladders

Wu, Changhao; Sui, Guiping; Thiruchelvam, Nikesh; Cuckow, Peter; Fry, CH

doi:10.1016/j.ceca.2006.01.002

Cited by 5 publications

(3 citation statements)

References 36 publications

(34 reference statements)

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“…Therefore, different in vitro function between human detrusor tissues from adult and pediatric bladders cannot be explained by a variation of detrusor contractile activation per se. Similar agonist contractile responses have also been measured when fetal and adult animal detrusor tissues were compared and when human detrusor responses from elderly (Ͼ70 yr) or younger patients with either normal or overactive bladders were compared (9,33). Thus, DSM function itself is similarly developed in pediatric and adult bladders and remains so even when aging bladder pathologies emerge.…”

Section: Discussionmentioning

confidence: 89%

“…The ratio of DSM to connective tissue (CT) is near unity in pediatric tissue but much greater in that from adults (17,19). Theoretically, this would decrease unit contractile performance and increase pediatric bladder wall stiffness compared with adults, depending on the collagen types in CT. Studies with term fetal animals have suggested that Ca 2ϩ regulation in detrusor myocytes is nearly complete (33), whereas tissue innervation remains incomplete (24,31).…”

mentioning

confidence: 99%

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Functional properties and connective tissue content of pediatric human detrusor muscle

Johal

Wood

Wagg

et al. 2014

American Journal of Physiology-Renal Physiology

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The functional properties of human pediatric detrusor smooth muscle are poorly described, in contrast to those of adult tissue. Characterization is necessary for more informed management options of bladder dysfunction in children. We therefore compared the histological, contractile, intracellular Ca2+ concentration responses and biomechanical properties of detrusor biopsy samples from pediatric (3-48 mo) and adults (40-60 yr) patients who had functionally normal bladders and were undergoing open surgery. The smooth muscle fraction of biopsies was isolated to measure proportions of smooth muscle and connective tissue (van Gieson stain); in muscle strips, isometric tension to contractile agonists or electrical field stimulation and their passive biomechanical properties; in isolated myocytes, intracellular Ca2+ concentration responses to agonists. Pediatric detrusor tissue compared with adult tissue showed several differences: a smaller smooth muscle-to-connective tissue ratio, similar contractures to carbachol or α,β-methylene ATP when corrected for smooth muscle content, and similar intracellular Ca2+ transients to carbachol, α,β-methylene ATP, raised K+ concentration or caffeine, but smaller nerve-mediated contractions and greater passive stiffness with slower stress relaxation. In particular, there were significant atropine-resistant nerve-mediated contractions in pediatric samples. Detrusor smooth muscle from functionally normal pediatric human bladders is less contractile than that from adult bladders and exhibits greater passive stiffness. Reduced bladder contractile function is not due to reduced smooth muscle contractility but to greater connective tissue deposition and to functional denervation. Significant atropine resistance in pediatric detrusor, unlike in adult tissue, demonstrates a different profile of functional neurotransmitter activation. These data have implications for the management of pediatric bladder function by therapeutic approaches.

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Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

Functional properties and connective tissue content of pediatric human detrusor muscle

Johal

Wood

Wagg

et al. 2014

American Journal of Physiology-Renal Physiology

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“…For example, a study comparing UBSM responses of fetal and adult sheep revealed altered muscarinic receptor sensitivity as the older group displayed higher potency for the agonist carbachol. Additionally, 10 µM α,β‐methylene ATP, a purinergic agonist, elicited significantly greater Ca 2+ transient currents in adult UBSM myocytes compared to their fetal counterpart suggesting greater P2X receptor expression in the adult (Wu et al, 2006). In line with previously mentioned studies, adult porcine UBSM (>40 weeks), when compared to juvenile UBSM (8–12 weeks), showed a higher number of muscarinic receptor binding sites as well as an increased potency to carbachol for stimulation of contractility (Wuest et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Age‐dependent decrease in TRPM4 channel expression but not trafficking alters urinary bladder smooth muscle contractility

et al. 2021

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During development, maturation, or aging, the expression and function of urinary bladder smooth muscle (UBSM) ion channels can change, thus affecting micturition. Increasing evidence supports a novel role of transient receptor potential melastatin‐4 (TRPM4) channels in UBSM physiology. However, it remains unknown whether the functional expression of these key regulatory channels fluctuates in UBSM over different life stages. Here, we examined TRPM4 channel protein expression (Western blot) and the effects of TRPM4 channel inhibitors, 9‐phenanthrol and glibenclamide, on phasic contractions of UBSM isolated strips obtained from juvenile (UBSM‐J, 5–9 weeks old) and adult (UBSM‐A, 6–18 months old) male guinea pigs. Compared to UBSM‐J, UBSM‐A displayed a 50–70% reduction in total TRPM4 protein expression, while the surface‐to‐intracellular expression ratio (channel trafficking) remained the same in both age groups. Consistent with the reduced total TRPM4 protein expression in UBSM‐A, 9‐phenanthrol showed lower potencies and/or maximum efficacies in UBSM‐A than UBSM‐J for inhibiting amplitude and muscle force of spontaneous and 20 mM KCl‐induced phasic contractions. Compared to 9‐phenanthrol, glibenclamide also attenuated both spontaneous and KCl‐induced contractions, but with less pronounced differential effects in UBSM‐A and UBSM‐J. In both age groups, regardless of the overall reduced total TRPM4 protein expression in UBSM‐A, cell surface TRPM4 protein expression (~80%) predominated over its intracellular fraction (~20%), revealing preserved channel trafficking mechanisms toward the cell membrane. Collectively, this study reports novel findings illuminating a fundamental physiological role for TRPM4 channels in UBSM function that fluctuates with age.

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