Email updates

Keep up to date with the latest news and content from BMC Urology and BioMed Central.

Open Access Technical advance

Development of an in vitro model to measure bioactivity of botulinum neurotoxin A in rat bladder muscle strips

Janneke IM van Uhm1*, Goedele MA Beckers1, Willem J van der Laarse2, Eric JH Meuleman1, Albert A Geldof13 and Jakko A Nieuwenhuijzen1

Author Affiliations

1 Department of Urology, VU University Medical Center, PO Box 7057, Amsterdam 1007 MB, The Netherlands

2 Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands

3 Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

For all author emails, please log on.

BMC Urology 2014, 14:37  doi:10.1186/1471-2490-14-37

Published: 15 May 2014



Botulinum toxin A (BoNT-A) is a new treatment modality in various causes of bladder dysfunction; like neurogenic detrusor overactivity and overactive bladder. The best technique of administrating BoNT-A in patients is unknown. A validated in vitro model could be used to investigate newer intravesical administration techniques of BoNT-A. In this study, we describe the development and validation of in vitro model to measure inhibitory effects of BoNT-A on bladder strip contractions.


Rat bladder strips were mounted in organ baths filled with Krebs’ solution. The strips were stimulated chemically (80 mM potassium chloride, 1 μM carbachol) and electrically (Electrical Field Stimulation (EFS) 100 shocks, 50 V, 20 Hz, every 3 minutes). The viability of the strips was measured by carbachol stimulation at the beginning and at the end of the experiments. The strips were incubated in various concentrations of BoNT-A (0.03, 0.2, 0.3 nM). Controls were incubated in Krebs’ solution only. The inhibition of strip contraction induced by EFS was measured. These measurements were statistically analyzed with a log-logistic model representing diffusion.


All strips remained viable during the experiments. Inhibition of strip contraction was observed after incubation with 0.3 nM BoNT-A. The measurements fitted to a log-logistic model describing diffusion of BoNT-A in the bladder strip. The parameters of the log-logistic model representing diffusion were significant for 0.3 nM BoNT-A. Incubation with 0.2 nM BoNT-A showed insignificant results for 2 out of 3 runs. Incubation with 0.03 nM BoNT-A did not result in significant inhibition of strip contractions.


An in vitro model was developed and validated in which the inhibitory effect of low concentrations of BoNT-A on bladder strip contractions can be measured.

Bladder; Botulinum toxin; Type A; In vitro