Characteristics of Spontaneous Activity in the Bladder Trigone

BackgroundDuring 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.ObjectivesTo characterise the cellular mechanisms that regulate and modify spontaneous activity in trigone smooth muscle.Design, setting, and participantsMuscle strips from the superficial trigone of male guinea-pigs were used for tension experiments and immunofluorescent studies.MeasurementsIn isolated trigonal cells, intracellular Ca2+ was measured by epifluorescence microscopy using the fluorescent Ca2+ indicator Fura-2.Results and limitationsSpontaneous 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 BKCa channel blocker iberiotoxin nor the SKCa 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.ConclusionsTrigone 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.