1 Collagenase dispersal of strips of rabbit urethra yielded, in addition to normal spindle-shaped smooth muscle cells, a small proportion of branched cells which resembled the interstitial cells of Cajal dispersed from canine colon. These were clearly distinguishable from smooth muscle in their appearance under the phase-contrast microscope, their immunohistochemistry and their ultrastructure. They had abundant vimentin filaments but no myosin, a discontinuous basal lamina, sparse rough endoplasmic reticulum, many mitochondria and a well-developed smooth endoplasmic reticulum. 2 Interstitial cells were non-contractile but exhibited regular spontaneous depolarisations in current clamp. These could be increased in frequency by noradrenaline and blocked by perfusion with calcium-free solution. In voltage clamp they showed abundant calcium-activated chloride current and spontaneous transient inward currents which could be blocked by chloride channel blockers. 3 The majority of smooth muscle cells were vigorously contractile when stimulated but did not show spontaneous electrical activity in current clamp. In voltage clamp, smooth muscle cells showed very little calcium-activated chloride current. 4 We conclude that there are specialised pacemaking cells in the rabbit urethra that may be responsible for initiating the slow waves recorded from smooth muscle cells in the intact syncitium.

Chronic obstructive pulmonary disease (COPD) is a debilitating heterogeneous disease characterised by unregulated proteolytic destruction of lung tissue mediated via a protease-antiprotease imbalance. In COPD, the relationship between the neutrophil serine protease, neutrophil elastase, and its endogenous inhibitor, alpha-1-antitrypsin (AAT) is the best characterised. AAT belongs to a superfamily of serine protease inhibitors known as serpins. Advances in screening technologies have, however, resulted in many members of the serpin superfamily being identified as having differential expression across a multitude of chronic lung diseases compared to healthy individuals. Serpins exhibit a unique suicide-substrate mechanism of inhibition during which they undergo a dramatic conformational change to a more stable form. A limitation is that this also renders them susceptible to disease-causing mutations. Identification of the extent of their physiological/pathological role in the airways would allow further expansion of knowledge regarding the complexity of protease regulation in the lung and may provide wider opportunity for their use as therapeutics to aid the management of COPD and other chronic airways diseases.

Isolated interstitial (“pacemaker”) cells from rabbit urethra were examined using the perforated-patch technique. Under voltage clamp at −60 mV, these cells fired large spontaneous transient inward currents (STICs), averaging −860 pA and >1 s in duration, which could account for urethral pacemaker activity. Spontaneous transient outward currents (STOCs) were also observed and fell into two categories, “fast” (1 s in duration). The latter were coupled to STICs, suggesting that they shared the same mechanism, while the former occurred independently at faster rates. All of these currents were abolished by cyclopiazonic acid, caffeine, or ryanodine, suggesting that they were activated by Ca²⁺release. Whend- myo-inositol 1,4,5-trisphosphate (IP₃)-sensitive stores were blocked with 2-aminoethoxydiphenyl borate, the STICs and slow STOCs were abolished, but the fast STOCs remained. In contrast, the fast STOCs were more nifedipine sensitive than the STICs or the slow STOCs. These results suggest that while fast STOCs are mediated by a mechanism similar to STOCs in smooth muscle, STICs and slow STOCs are driven by IP₃. These results support the hypothesis that pacemaker activity in the urethra is driven by the IP₃-sensitive store.

Specific classes of interstitial cells exist in visceral organs and have been implicated in several physiological functions including pacemaking and mediators in neurotransmission. In the bladder, Kit⁺interstitial cells have been reported to exist and have been suggested to be neuromodulators. More recently a second interstitial cell, which is identified using antibodies against platelet‐derived growth factor receptor‐α (PDGFR‐α) has been described in the gastrointestinal (GI) tract and has been implicated in enteric motor neurotransmission. In this study, we examined the distribution ofPDGFR‐α⁺cells in the murine urinary bladder and the relation that these cells may have with nerve fibres and smooth muscle cells. Platelet‐derived growth factor receptor‐α⁺cells had a spindle shape or stellate morphology and often possessed multiple processes that contacted one another forming a loose network. These cells were distributed throughout the bladder wall, being present in the lamina propria as well as throughout the muscularis of the detrusor. These cells surrounded and were located between smooth muscle bundles and often came into close morphological association with intramural nerve fibres. These data describe a new class of interstitial cells that express a specific receptor within the bladder wall and provide morphological evidence for a possible neuromodulatory role in bladder function.