Denervation supersensitivity of the rabbit urinary bladder to calcium ion

We investigated in vitro the supersensitivity of denervated rabbit bladder to Ca2+. Seven days after denervation achieved by bilateral sacral rhizotomy, the capacity of the denervated bladder increased by 2.2 times as compared with the control (126.3 to 277.3 ml.), and wet weight also increased 4.3 times (3.6 to 15.3 gm.). After 30 minutes incubation in normal Krebs' solution the denervated bladder strips showed significantly increased amplitude of contractions to the cumulative acetylcholine addition than the control. After incubation in normal Krebs' solution for 30 minutes, muscle strips were washed three times with Ca-free Krebs' solution and incubated 30 minutes in this solution. Cumulative Ca2+ replenishment (0.5 to 10 mM) induced dose-dependent contractions of the detrusor muscle strips in Ca2+-free Krebs' solution, where the contractions were significantly stronger in the denervated detrusor muscle than in controls. Pretreatment with 10(-6) M verapamil (Ca-entry blocker) eliminated the enhanced Ca2+-induced contractions of the denervated detrusor strips, while 10(-6) M procaine (Ca-induced Ca releasing blocker) only partially inhibited them. After depolarizing the cell membrane with 40 mM KCl, the Ca2+-induced contractions of the control strips were markedly enhanced but those of the denervated strips were not. These results demonstrate the supersensitivity of the denervated detrusor muscle to Ca2+. We conclude that hyperpermeability of the cell membrane to Ca2+ influx through calcium channels is responsible for supersensitivity of the denervated detrusor muscle to Ca2+.