Origin and modulation of spontaneous activity in the bladder trigone
Wednesday, 22 April 2007- The trigone provides a fixed, but controlled base to the bladder during filling, and relaxes just before emptying. Unlike dome and urethra, the trigone has a dual cholinergic and adrenergic innervation. Spontaneous activity might enable the trigone to adopt a state of sustained contracture.
A group of researchers in Germany and the UK assessed the interaction of different excitatory transmitters as well as the origin and modulation of trigonal spontaneity. Their work won the third prize for best abstract in non-oncology at the recent 24th Annual EAU Congress held in Stockholm, Sweden.
Intact muscle strips from the superficial trigone of male guinea-pigs were used for tension experiments and immunofluorescent studies. In isolated trigonal cells, intracellular calcium [Ca2+]i was measured by epifluorescence microscopy using the fluorescent Ca2+-indicator Fura-2.
The results showed that EFS contractions were enhanced by phenylephrine (PE, 3–10µM) by 6.4 ± 0.1-fold of control. PE augmented contractions induced by carbachol (1µm) to 4.0 ± 0.8-fold of control, while corresponding [Ca2+]i levels in single cells did not exceed 1.3 ± 0.2-fold of control. The protein kinase C inhibitor GF 109203X (5 µm) and the Rho-kinase inhibitor Y-27632 (5 µm) reduced the PE contracture to 37.3 ± 9.4 and 60.1 ± 12.4 % of control, respectively.
Spontaneous activity in trigonal single cells and strips was significantly higher compared to the bladder dome. 0-Ca+-solution and verapamil terminated spontaneity in cells as well as in the intact preparation. Cl--channel blocker niflumic acid was significantly effective in attenuating both single cell [Ca2+]i-transients and muscle contractions. Agonist stimulation (carbachol, phenylephrine) up-regulated the activity. Gap junction labelling (Cx43) was about 5 times denser in the trigonal than in the detrusor smooth muscle. Gap junction blocker 18-ß-GA had a depressing effect on spontaneous contractions in the trigone, but not the bladder dome.
The researchers concluded that muscarinic and adrenergic receptor activation exerts a strong synergistic effect in the trigone without similar changes to the [Ca2+]i transient, most likely mediated through Ca2+-sensitisation of contractile proteins. Similar to interstitial cells, trigonal smooth muscle cells employ membrane L-type-Ca2+- and Cl--channels to generate pronounced spontaneous activity. Extensive electrical coupling ensures its propagation and, thus, sustained contraction of the trigone during filling
Source: Roosen, A., Wu, C., Sui, et al., Ludwig Maximilians University, Dept. of Urology, Munich, Germany, University College London, Institute of Urology, London, United Kingdom, Poster Session, 3rd Prize Best Abstract for Non-Oncology, Abstract 216, “Origin and modulation of spontaneous activity in the bladder trigone,” 24th Annual EAU Congress, Stockholm, Sweden.