| Summary: | Lower Urinary tract diseases are an increasing problem in the ageing society, decreasing life quality and increasing cost of care. The underlying pathology of overactive bladder syndrome is not well understood, but has been linked with increased bladder contractility. Contractions of the smooth muscle in the bladder are localized to the bladder wall, but summed up affect the intravesical bladder pressure. In this thesis I explore contraction and movement initiation, propagation and the general bladder tone. Interstitial cells modulate spontaneous bladder activity by affecting initiation of contractions. To characterize them new markers are needed. I show expression of , Anol chloride channels on interstitial cells in juvenile , and adult rat bladder using molecular and immunolabelling techniques and presented data from bioinformatic search confirming expression of Anol in human bladders. In vitro and ex vivo recording showed that Anol blockers reduce phasic activity of rat bladder tissue. In isolated whole organ the frequency of pressure fluctuations was reduced, suggesting a role in the initiation of contractions. Spontaneous phasic activity in strips and whole organs differs between young and adult animals. In young animals, like in pathology, bladders show large amplitude low frequency phasic activity, while adult bladders have low amplitude high frequency contractions. Phasic activity changes are reflected also in the change of the bladder wall movements: from propagating contractions in young to multifocal asynchronous motile areas in adult animals. Propagation of contraction most likely happens via direct connections between the cells - the gap junctions. Blocking gap junctions in bladder tissue strips and isolated whole organ reduced the amplitude of bladder phasic activity. Effects of gap junction blockers on the tension (strips) and pressure (whole organ) measurements are comparable between young and adult animals. Microcontractions and micro elongations combined result in the phasic pressure fluctuations and are sensitive to changes in tone during relaxation by p-adrenoceptor agonist. These results show that bladder phasic activity and motility is composed of motile and non-motile areas, where initiation and propagation of contractions is possible when a bladder has a certain tone. Micromotions are a missing part of the bladder physiology. Chloride channel and gap junction blockers reduced spontaneous phasic activity and are a new direction in bladder disease pharmacology.
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