Etiology of bladder dysfunction secondary to partial outlet obstruction. Calcium disregulation in bladder power generation and the ability to perform work.
Similar to all smooth muscle, contraction of urinary bladder smooth muscle depends upon a rise in intracellular free calcium, which results from both calcium influx from extracellular spaces and calcium release from intracellular stores (calcium-induced calcium release [CICR]). Recent studies from our laboratory demonstrate that one of the major dysfunctions induced by partial outlet obstruction is a marked reduction in the participation of CICR (from IP3-sensitive and IP3-insensitive sites on the sarcoplasmic reticulum [SR]) during stimulation by both field stimulation (neurotransmitter release) and by direct muscarinic stimulation (bethanechol). Experimentally, rabbit urinary bladder function can be evaluated using an isolated whole bladder model. The current study utilizes the isolated whole bladder model to compare the effects of partial outlet obstruction on the responses to field stimulation and bethanechol with the responses of normal bladders following inhibition of CICR with the combination of thapsigargin+ryanodine. The parameters measured include the magnitude of pressure generation, rate of pressure generation, time to maximal pressure generation, percent volume emptied, rate of emptying, power generation, and work performed (both total work and work per ml emptied). Partial outlet obstruction resulted in virtually identical alterations in the responses of the bladder to stimulation (field stimulation and bethanechol) to that of inhibition of CICR by thapsigargin+ryanodine. Thus, these studies provide strong support for our hypothesis that the contractile dysfunctions secondary to partial outlet obstruction are directly related to a marked inhibition of the CICR component of the response to both field stimulation and bethanechol.
Levin
R M
RM
Division of Urology, University of Pennsylvania, USA.
Yu
H J
HJ
Kim
K B
KB
Longhurst
P A
PA
Wein
A J
AJ
Damaser
M S
MS
D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D007424:Intracellular Fluid / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D001743:Urinary Bladder / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*; D014563:Urodynamics / Q000502:physiology*
D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium