Calcium Ion Homeostasis in Urinary Bladder Smooth Muscle (original) (raw)
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Update on bladder smooth-muscle physiology
World Journal of Urology, 1994
The urinary bladder responds to distension induced by a number of different stresses with rapid and substantial increases in bladder mass and concomitant alterations in the contractile responses to neuronal stimulation, pharmacological simulation by autonomic agonists, and membrane depolarization. Furosemide, sucrose, or diabetes-induced diuresis, as well as outlet obstruction and overdistension all produce similar effects on the bladder. Accompanying the increases in bladder mass and contractile changes are increases in DNA synthesis and [3H]-thymidine uptake. Autoradiographic studies have localized the increased DNA synthesis following bladder distension initially to the urothelium, followed by slower increases in labelling of the lamina propria and extramural connective tissue. The net result of these compartmental differences in DNA synthesis is a reorganization of the structural relationships between smooth-muscle cells, the connective-tissue matrix, and the extrinsic connective-tissue lamina. This may contribute to the functional changes which occur after severe overdistension. Increases in the expression of heat-shock protein-70, basic fibroblast growth factor, N-ras, and c-myc, and decreases in transforming growth factor-beta occurred acutely after obstruction, suggesting that these changes may play a role in obstruction-induced bladder hypertrophy. Removal of the obstruction induces apoptosis of urothelial and connective tissue elements in the bladder, accompanied by increases in transforming growth factor-beta and decreases in basic fibroblast growth factor genes, and a reversal of the bladder dysfunction. Therefore the bladder hyperplasia after outlet obstruction and the regression following removal of the obstruction seem to be directly opposing processes governed by gene expression.
Calcium Regulation of Urinary Bladder Function
The Journal of Urology, 1997
Purpose: To investigate the effect of independently inhibiting calcium influx from extracellular sources and calcium release from intracellular stores on the ability of the urinary bladder to generate pressure and empty.
Morphology, Calcium Signaling and Mechanical Activity in Human Ureter
Journal of Urology, 2008
We determined the mechanisms of calcium signaling in the human ureter, and the relationship to peristaltic contractions and bundular structure in living tissue, thereby advancing the understanding of ureteral function in health and obstruction and reflux. Materials and Methods: Confocal imaging of 31 ureters was performed and simultaneous force and calcium measurements were made. Immunohistochemistry and Western blotting were also performed. Results: Confocal imaging showed a 3-dimensional network of smooth muscle bundles with no defined longitudinal or circular layers. Fast propagating Ca waves spread throughout the bundles, were closely associated with contraction and depended on L-type Ca channel entry. Immunohistochemistry and Western blotting demonstrated L-type Ca channels, Ca dependent K channels, sarcoplasmic reticulum Ca-adenosine triphosphatase isoforms 2 and 3, inositol triphosphate, and ryanodine receptors. Modulation of Ca and K channel activity was a potent mechanism for affecting Ca and force, whereas manipulation of the sarcoplasmic reticulum had little effect. Conclusions: To our knowledge this study represents the first measurements of Ca signals in the human ureter obtained during phasic contractions and in response to agonists. Results show that it is controlled by fast propagating Ca waves, which spread rapidly between the muscle bundles, producing regular contractions, and drugs that interfere with excitability or Ca entry through L-type Ca channels have profound effects on Ca signaling and contractility. These data are discussed in relation to the treatment of patients with suspected ureteral dysfunction using Ca entry blockers.
Neurourology and Urodynamics, 2005
Purpose: The decline in contractile properties is a characteristic feature of the dysfunctional bladder as a result of infravesical outlet obstruction. During clinical progression of the disease, smooth muscle cells undergo structural modi¢cations. Since adaptations to constant changes in length require a high degree of structural organization within the sarcolemma, we have investigated the expression of several proteins, which are involved in smooth muscle membrane organization, in specimens derived from normal and dysfunctional organs. Materials and Methods: Specimen from patients with urodynamically normal/equivocal (n ¼ 4), obstructed (n ¼ 2), and acontractile (n ¼ 2) bladders were analyzed relative to their structural features and sarcolemmal protein pro¢le. Results: Smooth muscle cells within the normal urinary bladder display a distinct sarcolemmal domain structure, characterized by ¢rm actin-attachment sites, alternating with £exible ''hinge'' regions. In obstructed bladders, foci of cells displaying degenerative sarcolemmal changes alternate with areas of hypertrophic cells in which the membrane appears una¡ected. In acontractile organs, the overall membrane structure remains intact, however annexin 6, a protein belonging to a family of Ca 2þ-dependent, ''membrane-organizers, '' is downregulated. Conclusion: Degenerative changes in smooth muscle cells, which are chronically working against high resistance, are preferentially located within the actin-attachment sites. In acontractile bladders, the downregulation of annexin 6 might have a bearing on the ¢ne-tuning of the plasma membrane during contraction/relaxation cycles.
Journal of Cellular and Molecular Medicine, 2012
The contractile properties of the urinary bladder are changed by the conditions of normal development and partial bladder outlet obstruction. This change in the contractile phenotype is accompanied by changes in the regulatory cascades and filaments that regulate contractility. This review focuses on such changes during the course of normal development and in response to obstruction. Our goal is to discuss the experimental evidence that has accumulated from work in animal models and correlate these findings with the human voiding phenotype.
Journal of Autonomic Pharmacology, 2001
1 Despite the growing social interest in human urinary tract disorders, the aetiology of detrusor instability remains poorly understood. Myogenic and neural impairment of detrusor activity caused by CNS or autonomic injuries can results in dysfunctions of normal voiding of the bladder such as urinary incontinence. 2 The contractility of human detrusor smooth muscle is critically dependent on acetylcholineinduced muscarinic receptor activation. Biochemical and functional in vivo and in vitro studies suggest the presence of an heterogeneous population of muscarinic receptor subtypes (M 1 -M 4 ) localized at muscular and neutral sites. There is increasing evidence on the prejunctional autoand hetero-regulation of acetylcholine release from parasympathetic nerve endings in modulating detrusor muscle contraction during micturition. 3 Activation of P2X purinoreceptors closely associated with the parasympathetic varicosities seems to be implicated to varying extent in the contractility in normal or instable human detrusor. Interestingly, P2X 1 subtype expression on smooth muscle increases considerably in the symptomatically obstructed bladder. A striking absence of P2X 3 and P2X 5 subtypes was observed in the cholinergic innervation of detrusor from patients with urgent incontinence. Thus, it is likely that alteration of the neural acetylcholine control can play a critical role in pathological states. 4 If the failures in storage and voiding can be recognized urodynamically, considerable difficulties remain in investigating the underlying functional changes especially because the study of the pathophysiology requires techniques that can be justified in animals but not in humans. 5 Recently, to solve this problem an alternative technique using human smooth muscle cells in culture has been developed. Human cell lines may be relevant in investigating the molecular pathways in physiological and pathological conditions. 6 The potential development of novel molecular therapeutic strategies such as gene therapy and tissue engineering is also discussed.