European Urology

Abstract

Background

During bladder filling, the trigone contracts help keep the ureteral orifices open and the bladder neck shut. The trigone generates spontaneous activity as well as responding to neuromuscular transmitters, but the relationship between these phenomena are unclear.

Objectives

To characterise the cellular mechanisms that regulate and modify spontaneous activity in trigone smooth muscle.

Design, setting, and participants

Muscle strips from the superficial trigone of male guinea-pigs were used for tension experiments and immunofluorescent studies.

Measurements

In isolated trigonal cells, intracellular Ca²⁺ was measured by epifluorescence microscopy using the fluorescent Ca²⁺ indicator Fura-2.

Results and limitations

Spontaneous intracellular Ca²⁺ transients and contractions were observed in trigonal single cells and strips and were significantly higher compared to the bladder dome. Ca-free superfusate and verapamil terminated spontaneity. T-type Ca²⁺ channel block with NiCl₂ depressed slightly Ca²⁺ transients but not spontaneous contractions. Neither the BK_Ca channel blocker iberiotoxin nor the SK_Ca channel blocker apamin had any effect on single cell activity. By contrast, the Cl⁻ channel blocker niflumic acid attenuated significantly both Ca²⁺ transients and muscle contractions. Agonist stimulation (carbachol, phenylephrine) up-regulated activity. Gap junction labelling (Cx43) was approximately 5 times denser in the trigone than in detrusor smooth muscle. The gap junction blocker 18-ß-glycyrrhetinic acid modulated spontaneous contractions in the trigone but not in the bladder dome.

Conclusions

Trigone myocytes employ membrane L-type-Ca²⁺ channels and Cl⁻ channels to generate spontaneous activity. Intercellular electrical coupling ensures its propagation and, thus, sustains contraction of the whole trigone.

Take Home Message

Trigonal smooth muscle cells employ membrane L-type-Ca²⁺ and Cl⁻ channels to generate pronounced spontaneous activity. Extensive electrical coupling ensures propagation throughout the whole trigone and its sustained contraction, which in turn may enable the trigone to keep the orifices open and the bladder neck shut during bladder filling.