![]() Urothelial cells have neuronal-like properties and release factors such as ATP ( 15), nitric oxide (NO Potential structures within the bladder wall that could regulate activity include the urothelial layer, lamina propria myofibroblasts (LPM), and interstitial cell (IC)-like cells found throughout the bladder wall. These observations indicate an intrinsic mechanism in the bladder that controls spontaneous activity of detrusor smooth muscle. This may contribute to the increase in intrinsic contractions in bladder pathologies such as outlet obstruction or spinal cord damage, where there are significant changes to the tissue architecture and decreased or lost innervation of the bladder ( 13). This indicates there is an inhibitory control from the spinal cord over intrinsic bladder activity, but does not appear to be a driving force. This has also been demonstrated with in vitro brain stem-spinal cord-bladder preparations in neonatal rats, where when the connection from the spinal cord to the bladder is severed there is an increase in the amplitude of intrinsic contractions of the bladder ( 45, 46). There may also be influence from the central nervous system (CNS) over intrinsic activity as the addition of a ganglionic blocker increases the amplitude of intrinsic bladder contractions ( 30), leading to the theory that they may play a role in pathological conditions where CNS inhibition over the lower urinary tract has become compromised. Intrinsic contractions have been demonstrated to be more prominent in neonatal rats than adults ( 33), and these predominant contractions reemerge in pathology (e.g., detrusor overactivity), increasing their amplitude in response to bladder filling. ![]() This is supported by observations that detrusor smooth muscle has spontaneous Ca 2+ transients or Ca 2+ sparks ( 6, 22), which are thought to contribute to the excitability of the cell. These contractions seem to occur in normal healthy bladders during the filling phase when the efferent nerves are effectively silent, and thus intrinsic activity was initially hypothesized to be myogenic in origin, possibly as a mechanism to keep the bladder wall taut against the growing bolus of urine as the bladder fills. However, intrinsic bladder contractile activities (observed in vitro and in vivo), which are not large enough to cause micturition (thus also referred to as nonvoiding contractions), have been described from various species ( 30, 44). In summary, we suggest an urotheliogenic origin for intrinsic activity, where structures within the mucosal layer organize and thereby enhance intrinsic detrusor contractions.Ĭontractile activity of the bladder is a result of coordinated activation of the embedded efferent nerves to activate muscarinic and purinergic receptors on the detrusor smooth muscle, inducing a micturition response. Optical mapping of mucosa-denuded sheets, where enhanced spontaneous activity was abolished, or application of 1 μM nifedipine to remove smooth muscle signals, but not the mucosal signals, shows that intrinsic activity in pathological bladders is driven by the mucosal layer. Partial removal of the mucosa decreased the amplitude of the intrinsic contractions and decreased the response to stretch or arecaidine. The magnitude of intrinsic contractions could be enhanced by stretch or low-dose arecaidine (50 nM), a muscarinic-specific agonist. Normal bladders showed multiple initiation sites across the mucosal surface, whereas SCT bladders showed only one or two fixed initiation sites localized to the dome. The difference in contractile activity was mirrored in the Ca 2+ and membrane potential maps of bladder sheets. In contrast, in the SCT animals there were high-amplitude, low-frequency contractions that displayed an organized spread of membrane potential and intracellular Ca 2+. Both normal adult and SCT rat bladders displayed intrinsic contractions, where normal bladders showed low-amplitude, high-frequency contractions with disorganized patterns of activity. Normal adult and spinal cord-transected (SCT) rat bladders were stained with Ca 2+- and voltage-sensitive dyes, and optical activity generated from intrinsic contractions was mapped from the mucosal surface of whole bladder sheets. We examined the modulation of intrinsic (i.e., spontaneous) detrusor contractions by the urothelium and the lamina propria through optical mapping approaches.
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