Abstract
Bladder dysfunction is characterized by urgency, frequency (pollakisuria, nocturia), and dysuria and may lead to urinary incontinence. Most of these symptoms can be attributed to disturbed bladder sensitivity. There is growing evidence that, besides the urothelium, suburothelial interstitial cells (suICs) are involved in bladder afferent signal processing. The massive expansion of the bladder during the filling phase implicates mechanical stress delivered to the whole bladder wall. Little is known about the reaction of suICs upon mechanical stress. Therefore, we investigated the effects of mechanical stimulation in cultured human suICs. We used fura-2 calcium imaging as a major physiological readout. We found spontaneous intracellular calcium activity in 75 % of the cultured suICs. Defined local pressure application via a glass micropipette led to local increased calcium activity in all stimulated suICs, spreading over the whole cell. A total of 51% of the neighboring cells in a radius of up to 100 µm from the stimulated cell showed an increased activity. Hypotonic ringer and shear stress also induced calcium transients. We found an 18-times increase in syncytial activity compared to unstimulated controls, resulting in an amplification of the primary calcium signal elicited in single cells by 50%. Our results speak in favor of a high sensitivity of suICs for mechanical stress and support the view of a functional syncytium between suICs, which can amplify and distribute local stimuli. Previous studies of connexin expression in the human bladder suggest that this mechanism could also be relevant in normal and pathological function of the bladder in vivo.
Highlights
The urinary bladder has a dual function, periodical stretching during the filling phase and exhibiting mass contraction for micturition
While the peaks varied in amplitude and frequency, their morphology was remarkably consistent; a fast rise of [Ca2+]i followed by a slow signal decay (Figure 2) was observed
We here demonstrated for the first time that mechanical stimulation of cultured human suburothelial interstitial cells evoked intracellular calcium transients
Summary
The urinary bladder has a dual function, periodical stretching during the filling phase and exhibiting mass contraction for micturition. Many details of the lower urinary tract function have been learned from diseased states in humans and in animal models, such as bladder outlet obstruction (BOO) and overactive bladder (OAB), and interstitial cystitis/bladder pain processing in the bladder wall is still enigmatic. Many details of the lower urinary tract function have been learned from diseased states in humans and in animal models, such as bladder outlet obstruction (BOO), overactive bladder (OAB), and interstitial cystitis/bladder pain syndrome (IC/BPS) [3,4]. Recent comparative studies on ICs in human and the major laboratory animals suggest that the understanding of the roles of ICs partly needs revision [7,9,10]
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