The Use of the Isolated Mouse Whole Bladder for Investigating Bladder Overactivity

Abstract

The isolated mouse whole bladder was used to study in vitro bladder overactivity evoked by intramural nerve sensitization with bradykinin, mimicking neurogenic bladder overactivity secondary to bladder inflammation. Intravesical pressure responses to intramural electrical stimulation of intramural nerves were measured under isovolumetric condition. Validation showed that carbachol produced a dose-response curve closely mirroring that observed in the isolated muscle strips and demonstrated the dual nature of electrically evoked neurotransmission, consisting of a cholinergic component largely mediated by M 3 receptors and a purinergic component mediated by P2X receptors. ATP generated a biphasic dose-response curve, suggesting that the P2X receptors may be heterogeneous in distribution. Characterization of bradykinin receptors showed bradykinin to be extremely potent in exciting the bladder, producing a dose-response curve with an EC 50 of 90 nM, and bradykinin also enhanced electrically evoked bladder contractions. These effects were inhibited by the B 2 receptor antagonist HOE 140 (D-Arg 0 -Arg

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

“…The peak contraction pressure change of the ChR2-expressing bladder by light (6.3 mW) was comparable to those by other stimulants such as carbachol (3 μM), a cholinergic agonist, and electrical field stimulation (50 VDC with 0.1 ms pulse duration at 20 Hz) (Fig. 3e), and was within the physiological range of voiding bladder pressure (40~50 cmH 2 O) of various species, including humans1 and rodents15.…”

“…The stimulation parameters of EFS were 50VDC, 0.1ms pulse duration, and 20 Hz, as previously described15.…”

The extracorporeal perfusion of the female pig detrusor as an experimental model for the study of bladder contractility

“…They concluded that this response is dependent mainly on depolarization of the cell membranes and an influx of extracellular Ca 2þ , and also suggest that this depolarizing response may be due to inactivation of ATP-sensitive potassium channels through muscarinic activation of protein kinase C. 49 Validation experiments showed that external application of carbachol induced a dose response curve that compares very well with that produced in isolated muscle strips. 10 There is considerable interest in the ion channels involved in generating the spontaneous activity in the detrusor. Much of this interest is driven by the need to develop drugs to treat the symptoms of bladder overactivity, which include urgency and urge incontinence.…”

Neuropeptides in Lower Urinary Tract Function

“…The bradykinin/receptors system plays an important role in normal micturition reflexes as well as in pathology (Lecci et al, 1995; Belichard et al, 1999; Lecci et al, 1999; Meini et al, 2000; Chopra et al, 2005; Fabiyi and Brading, 2006). Kinins are small peptides (8–10 amino acids) produced in plasma or in tissues at the sites of inflammation or tissue damage (Bhoola et al, 1992).…”