PURPOSE: To determine the mechanisms of botulinum neurotoxin A (Metabiologics, Madison, Wisconsin) induced inhibition of bladder activity we examined the effect of botulinum neurotoxin A on detrusor contractile responses to the activation of L-type voltage-gated Ca(2+) channels, and efferent and afferent nerve terminals in the rat bladder. MATERIALS AND METHODS: Rat bladder strips were incubated for 3 hours with different concentrations of botulinum neurotoxin A (0.3 to 100 nM). We examined the effect of botulinum neurotoxin A on detrusor contractility in response to activation of L-type voltage-gated Ca(2+) channels, and efferent and afferent nerve terminals induced by 70 mM KCl, electrical field stimulation and 1 μM capsaicin, respectively. RESULTS: Botulinum neurotoxin A inhibited electrical field stimulation induced contractions at a concentration of 10 nM or higher. The maximal inhibition at 100 nM was 70% compared to that of control strips. KCl induced contractions, which were sensitive to nifedipine, were significantly inhibited by incubation with botulinum neurotoxin A at a concentration of 3 nM or higher. Maximal inhibition at 100 nM was 30% compared to that of control strips. Capsaicin induced contractions were not inhibited by 3-hour incubation but they were significantly inhibited by overnight incubation with 100 nM botulinum neurotoxin A (30% compared to control strips). Carbachol induced contractions were not altered by incubation with botulinum neurotoxin A. CONCLUSIONS: The order of inhibitory potency of botulinum neurotoxin A was efferent nerve terminals >L-type voltage-gated Ca(2+) channels >afferent nerve terminals. Since the inhibitory effects on L-type voltage-gated Ca(2+) channels and efferent nerve terminals were observed at similar botulinum neurotoxin A concentrations, the inhibitory effect of botulinum neurotoxin A on L-type voltage-gated Ca(2+) channels may have an important role in regulating and stabilizing bladder activity.
PURPOSE: To determine the mechanisms of botulinum neurotoxin A (Metabiologics, Madison, Wisconsin) induced inhibition of bladder activity we examined the effect of botulinum neurotoxin A on detrusor contractile responses to the activation of L-type voltage-gated Ca(2+) channels, and efferent and afferent nerve terminals in the rat bladder. MATERIALS AND METHODS:Rat bladder strips were incubated for 3 hours with different concentrations of botulinum neurotoxin A (0.3 to 100 nM). We examined the effect of botulinum neurotoxin A on detrusor contractility in response to activation of L-type voltage-gated Ca(2+) channels, and efferent and afferent nerve terminals induced by 70 mM KCl, electrical field stimulation and 1 μM capsaicin, respectively. RESULTS: Botulinum neurotoxin A inhibited electrical field stimulation induced contractions at a concentration of 10 nM or higher. The maximal inhibition at 100 nM was 70% compared to that of control strips. KCl induced contractions, which were sensitive to nifedipine, were significantly inhibited by incubation with botulinum neurotoxin A at a concentration of 3 nM or higher. Maximal inhibition at 100 nM was 30% compared to that of control strips. Capsaicin induced contractions were not inhibited by 3-hour incubation but they were significantly inhibited by overnight incubation with 100 nM botulinum neurotoxin A (30% compared to control strips). Carbachol induced contractions were not altered by incubation with botulinum neurotoxin A. CONCLUSIONS: The order of inhibitory potency of botulinum neurotoxin A was efferent nerve terminals >L-type voltage-gated Ca(2+) channels >afferent nerve terminals. Since the inhibitory effects on L-type voltage-gated Ca(2+) channels and efferent nerve terminals were observed at similar botulinum neurotoxin A concentrations, the inhibitory effect of botulinum neurotoxin A on L-type voltage-gated Ca(2+) channels may have an important role in regulating and stabilizing bladder activity.
Authors: Ann T Hanna-Mitchell; Amanda S Wolf-Johnston; Stacey R Barrick; Anthony J Kanai; Michael B Chancellor; William C de Groat; Lori A Birder Journal: Neurourol Urodyn Date: 2013-10-26 Impact factor: 2.696
Authors: Janneke I M van Uhm; Goedele M A Beckers; Willem J van der Laarse; Eric J H Meuleman; Albert A Geldof; Jakko A Nieuwenhuijzen Journal: BMC Urol Date: 2014-05-15 Impact factor: 2.264
Authors: Mark Elliott; Jacquie Maignel; Sai Man Liu; Christine Favre-Guilmard; Imran Mir; Paul Farrow; Fraser Hornby; Sandra Marlin; Shilpa Palan; Matthew Beard; Johannes Krupp Journal: PLoS One Date: 2017-10-05 Impact factor: 3.240