Related Experiment Video
Updated: May 23, 2026
Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology
Published on: August 18, 2014
Botulinum neurotoxin serotype A suppresses neurotransmitter release from afferent as well as efferent nerves in the
Youko Ikeda1, Irina V Zabbarova, Lori A Birder
1Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Background:
Botulinum neurotoxin A (BoNTA), which alleviates overactive bladder symptoms, is thought to act predominantly via the inhibition of transmitter release from parasympathetic nerves. However, actions at other sites such as afferent nerve terminals are possible.
Objective:
To evaluate the effects of BoNTA on bladder afferent neuropeptide release and firing.
Design, Setting, And Participants:
One side of the bladder of control and chronic (1-2 wk) spinal cord transected (SCT; T(8)-T(9)) adult female mice was injected with BoNTA (0.5 U/5 μl saline). After 48 h, bladders with L(6)-S(2) spinal nerves were prepared for in vitro recordings.
Outcome Measurements And Statistical Analysis:
In bladder preparations, tension and optical mapping of Ca(2+) transients were used to measure intrinsic contractions, those evoked by capsaicin or the electrical stimulation of spinal nerves. Afferent firing was evoked by stretch or intrinsic bladder contractions. The numbers of responding units and firing rates were measured. Animal numbers were used to detect moderate to large between-group differences based on Cohen's criteria. Two-way analysis of variance was used to test spatial/temporal differences in Ca(2+) signals as mean plus or minus standard deviation. Differences between data sets were tested with the student t test and skewed data sets with a Mann-Whitney U test (significant when p<0.05).
Results And Limitations:
In control and SCT bladders, BoNTA treatment decreased the contractions evoked by electrical stimulation of spinal nerves without altering intrinsic contractions. Afferent firing on untreated sides in response to stretch/intrinsic contractions was increased in SCTs versus controls. On BoNTA-treated sides, afferent firing rates were greatly attenuated in response to mechanical stimulation as were the capsaicin-evoked optical signals mediated by neuropeptide release.
Conclusions:
SCT caused an increased sensitivity of afferent nerves to mechanical stimulation that was reduced by BoNTA treatment. Increased intrinsic activity after SCT was unaffected by the toxin. Thus BoNTA suppresses neurogenic detrusor overactivity by targeting afferent as well as efferent pathways in the bladder.
More Related Videos
10:30A High-throughput-compatible FRET-based Platform for Identification and Characterization of Botulinum Neurotoxin Light Chain Modulators
Published on: December 27, 2013
06:36A Decentralized (Ex Vivo) Murine Bladder Model with the Detrusor Muscle Removed for Direct Access to the Suburothelium during Bladder Filling
Published on: November 28, 2019
Related Concept Videos
01:26Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
The binding of dantrolene to the RYR1...
01:26Neurochemical Transmission: Sites of Drug Action
01:30Indirect-Acting Cholinergic Agonists: Pharmacological Actions
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
01:29Neuromuscular Junction And Blockade
01:21Drugs Affecting Neurotransmitter Release or Uptake
01:26Chemical Synapses
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...