Phasic changes in pressure have been reported to occur in the bladder which are not associated with micturition. Spontaneous intravesical pressure changes can be recorded from bladders in vitro or bladders in vivo isolated from the central nervous system suggesting that the bladder itself is capable of autonomous activity. Experiments using isolated cells and muscle strips indicate that the smooth muscle can generate spontaneous activity. Whether this is the origin of phasic changes in the intact organ remains unknown. The present study set out to establish the presence and characteristics of autonomous activity in the isolated guinea pig bladder. Multiple-point motion analysis and concurrent intravesical pressure recording were used to identify and quantify spontaneous and evoked activity. Highly complex autonomous activity was observed in unstimulated bladders. This activity comprised localised micro-contractions in single or multiple discrete regions, waves of activity and micro-stretches. Low-amplitude phasic 'micro-transients' were seen in the intravesical pressure trace in association with micro-contractions. Incremental increases in the intravesical volume recruited additional areas of activity. Atropine and tetrodotoxin had no effect on the micro-transients or micro-contractions. Exposure to the muscarinic agonist arecaidine (10-300 nM) initially increased the incidence of micro-contractions which subsequently became co-ordinated into phasic pressure rises and contraction waves, interspersed with periods of total quiescence. The findings describe the generation and co-ordination of autonomous activity in the bladder wall and also demonstrate complex phasic activity. This approach has shown the importance of assessing the integrative properties of the entire organ in studies of the physiology and patho-physiology of the bladder.

Incontinence and the generation of excessive sensory urges are common problems that can seriously influence the quality of life of both men and women. The underlying causes have in some instances been associated with uncontrolled bladder activity. However, the mechanisms generating such activity are still poorly understood and pharmacological tools to control it remain relatively ineffective. There are no effective treatments for bladder overactivity possibly because the bladder mechanisms are not understand or targeted. The purpose of this short review is to raise questions and re‐visit ideas from some older possibly forgotten and neglected publications, but which may shed new light on this problem.

Spontaneous localised propagating waves of contraction and localised stretches have been reported to occur in the isolated whole bladder of the guinea pig. The physiological role and the cellular processes underlying these events are unknown. In order to gain insight into the mechanisms generating this complex activity, experiments were performed to examine and compare the responses of the whole bladder preparation to (i) the muscarinic agonists carbachol and arecaidine, (ii) the nicotinic ligand lobeline and (iii) nerve stimulation. High concentrations of the muscarinic agonists (>3 μM) induced a slow rise in intra‐vesical pressure upon which were superimposed pressure transients, while low concentrations (< 300 nM) induced only phasic rises in pressure. One interpretation of these data is that there are two separate mechanisms activated by muscarinic agonists: one generating contracture and the other phasic activity. Immunocytochemical staining revealed M3 muscarinic receptors on smooth muscle cells within trabeculae and a second population of positive cells in the sub‐urothelial layer. This observation raises the possibility that the actions of muscarinic agonists are a consequence of activating different cell types. Lobeline (1‐60 μM) activated phasic contractions but did not cause a rise in basal pressure. Atropine did not inhibit the lobeline‐induced responses but abolished the muscarinic responses. Also, hexamethonium or tetrodotoxin did not affect the lobeline‐induced responses. These observations suggest that the mechanism generating phasic activity is activated by a nicotinic stimulus that does not involve ganglia, nerves or the neuromuscular junction. Stimulation of the bladder nerve at frequencies between 20 and 30 Hz for 5 s resulted in a rapid rise in intra‐vesical pressure. Prolonged nerve stimulation (10‐200 s) at frequencies between 1 and 10 Hz activated phasic rises in pressure. Low frequency nerve stimulation increased the frequency of agonist‐induced phasic activity. Thus, nerve stimulation can also produce two forms of activity and low frequency stimulation can augment the processes generating phasic activity. These observations suggest that there are two distinct types of bladder activity: global contractions involving most of the bladder wall and phasic contractions comprising propagating waves of contraction. The mechanisms generating these contractile events appear to be different and they may involve cells located in different regions of the bladder. The nature of these mechanisms and their possible physiological significance is discussed.

(MMD) method, using eight electrodes mounted on a Silastic balloon; local displacements of the electrodes were recorded as changes in electrical resistance, which were used to compute changes in the distance between each pair of electrodes. RESULTSIn two of the six volunteers, micromotions were seen in the extraperitoneal (ventral) portion of the bladder. Women with increased sensation on filling cystometry had a significantly higher prevalence of localized activity than the control group during MMD recording. The localized activity was more sustained and at a higher frequency than in asymptomatic women. All nine women reporting urinary urgency during MMD recording had localized contractile activity, while only four had phasic increases in detrusor pressure during the episodes of urgency.

OBJECTIVE To identify cells which might contribute to the complex physiological responses of the guinea‐pig bladder, and specifically to describe the distribution and types of cell in the bladder wall of the guinea pig which respond to nitric oxide (NO) with an increase in intracellular cGMP, i.e. putative interstitial cells (ICs). MATERIALS AND METHODS The whole bladder was removed from 11 male guinea pigs killed by cervical dislocation. Sections of the bladder wall, from the dome lateral wall and base, were isolated and incubated separately in Krebs’ solution at 36 °C, gassed with 95% O2 and 5% CO2, and containing 1 mmol/L of the nonspecific phosphodiesterase inhibitor isobutyl‐methyl‐xanthene. Individual pieces of tissue were then exposed to 100 µmol/L of the NO donor NONOate for 10 min; control tissues remained in Krebs’ solution. Tissues were then fixed in 4% paraformaldehyde and processed for immunohistochemistry. cGMP and neuronal NO synthase (nNOS) were subsequently visualized using appropriate primary and secondary antibodies. RESULTS Cells responding to NO with an increase in cGMP were detected in the dome, lateral wall and base, with positive cells in the thin outer surface of the wall (muscle coat), associated with muscle bundles in an outer layer of muscle, and in a region immediately beneath the urothelium. These cells (not urothelium, smooth muscle or vascular) are described as interstitial cells. Superficial urothelial umbrella cells were apparent and were strongly cGMP‐positive. A high density of interstitial cells was associated with muscle bundles on the outer aspects of the wall, while few cells were detected on inner bundles. Thus there appeared to be two distinct types of muscle, inner and outer, with no obvious orientation of the fibres in each layer. Both muscle groups contained fibres expressing nNOS. In the outer muscle layer most of these fibres co‐localized with cGMP, suggesting that different populations of nerves innervate each layer. There were more nNOS‐positive fibres in the base of the bladder than in the dome. Three populations of cGMP‐positive interstitial cells were associated with the outer muscle layer; cells in the outer surface (muscle coat interstitial cells, MC‐ICs), cells on the surface of the bundles (superficial, SM‐ICs) and cells within the muscle bundles (intramuscular, IM‐ICs). The IM‐ICs form a network in close apposition to the smooth muscle cells while the SM‐ICs may connect adjacent muscle bundles and connect to the MC‐ICs. Thus, there is a network linking potentially the muscle cells in the outer muscle bundles. cGMP‐positive cells were also detected in the suburothelial layer (suburothelial, SU‐ICs) which had a different structure to the cells associated with muscle, had a oval cell bodies with bifurcating processes and appeared to form a complex network; they were prevalent in the base and virtually absent in the dome. CONCLUSIONS There are structures within the bladder wall that can be identified and categorized by the ability of the constituent cells to in...