CALCIUM REGULATION OF URINARY-BLADDER FUNCTION

Purpose: To investigate the effect of independently inhibiting calcium influx from extracellular sources and calcium release from intracellu lar stores on the ability of the urinary bladder to generate pressure and empty. Materials and Methods: Rabbit bladders were mounted in an i n vitro whole organ bath and filled with 15 mi. saline. Each bladder w as incubated separately in Tyrode's solution, with diltiazem (10 mu M) , to block extracellular calcium influx, or with thapsigargin (40 mu M ) and ryanodine (80 mu M), to block the uptake and release of calcium from the sarcoplasmic reticulum. The bladder was then stimulated isome trically with field stimulation (32 Hz), and to empty with field stimu lation and with bethanechol (250 mu M), independently. During stimulat ion, transmural pressure and volume emptied were measured. From these, flow rate, power, and external mechanical work were calculated. Resul ts: In the presence of diltiazem, the time to maximal pressure decreas ed while the rate of pressure generation increased. This results from increased participation of intracellular calcium release, which occurs rapidly and near the smooth muscle filaments, decreasing the diffusio n time. In the presence of thapsigargin and ryanodine the maximal rate of pressure generation was decreased, due to the increased diffusion time required for calcium to move to the muscle filaments from extrace llular sites. Conclusions: The current study demonstrates that bladder pressure generation and emptying are dependent upon both an influx of calcium through L-type calcium channels (inhibited by diltiazem) and the stimulated release of calcium from the SR (inhibited by thapsigarg in and ryanodine).