Effect of thapsigargin on the contractile response of the normal and obstructed rabbit urinary bladder

Excitation-contraction coupling is achieved by translocation of calcium from the extracellular space as well as by the release of calcium from intracellular stores. Thapsigargin has been shown to selectively block the sarcoplasmic Ca-ATPase, thereby preventing the reuptake of calcium into intracellular stores and the participation of these calcium storage sites in the contractile response to stimulation. The current study determined the effect of thapsigargin on the contractile response to field stimulation, bethanechol, and KCl in control rabbit bladders and bladders obtained from rabbits subjected to partial outlet obstruction. Partial bladder outlet obstruction resulted in a marked increase in bladder mass and in significant decreases in the contractile response to field stimulation, bethanechol, and KCl. Thapsigargin (5-40 microM) had no effect on the contractile responses of bladder strips isolated from control rabbits to field stimulation, bethanechol, or KCl. However, bladder strips isolated from obstructed rabbits showed a significant concentration-dependent decrease in the contractile response to field stimulation in the presence of thapsigargin. Thapsigargin had no effect on the contractile responses of bladder strips isolated from obstructed rabbits to either bethanechol or KCl. In general, the data described in this study support our current hypothesis: as smooth muscle cells enlarge (hypertrophy) and the cell volume increases, there is an increased dependence on the release of intracellular calcium from the sarcoplasmic reticulum to mediate the contractile response to field stimulation.