Calcium regulation of urinary bladder function.
OBJECTIVE
To investigate the effect of independently inhibiting calcium influx from extracellular sources and calcium release from intracellular stores on the ability of the urinary bladder to generate pressure and empty.


METHODS
Rabbit bladders were mounted in an in vitro whole organ bath and filled with 15 ml. saline. Each bladder was incubated separately in Tyrode's solution, with diltiazem (10 microM), to block extracellular calcium influx, or with thapsigargin (40 microM) and ryanodine (80 microM), to block the uptake and release of calcium from the sarcoplasmic reticulum. The bladder was then stimulated isometrically with field stimulation (32 Hz), and to empty with field stimulation and with bethanechol (250 microM), independently. During stimulation, transmural pressure and volume emptied were measured. From these, flow rate, power, and external mechanical work were calculated.


RESULTS
In the presence of diltiazem, the time to maximal pressure decreased 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 diffusion 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 extracellular 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 thapsigargin and ryanodine).
Damaser
M S
MS
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, USA.
Kim
K B
KB
Longhurst
P A
PA
Wein
A J
AJ
Levin
R M
RM
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D010277:Parasympathomimetics / Q000494:pharmacology; D011312:Pressure; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D010277:Parasympathomimetics; D018723:Bethanechol; D012433:Ryanodine; D019284:Thapsigargin; D004110:Diltiazem; D002118:Calcium