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        The Frequency-Dependence of Pre- and Postganglionic Nerve Stimulation of Pig and Rat Bladder

        Darryl Kitney,John Crook,Basu Chakrabarty,Anthony Kanai,Bahareh Vahabi,Thelma Lovick,Christopher Fry 대한배뇨장애요실금학회 2021 International Neurourology Journal Vol.25 No.3

        Purpose: The urinary bladder generates phasic contractions via action potentials generated in pre- and then postganglionic neurons. Whilst the frequency-dependence of postganglionic neurons to generate contractions has been quantified, the dynamic range of preganglionic neurons is less clear and if intramural ganglia exert frequency-dependent modulation of transmission between pre- and postganglionic neurons. The phosphodiesterase type 5 inhibitor sildenafil reduces neurotransmitter release from postganglionic fibres to detrusor smooth muscle and an additional question was if there was also a preganglionic action. This study aimed to compare the frequency range of bladder contractile activation by pre- and postganglionic stimulation in pig and rat bladders and if sildenafil exerted additional preganglionic actions. Methods: An arterially-perfused ex vivo pig bladder preparation was used for preganglionic (pelvic nerve) and mixed preand postganglionic (direct bladder wall) stimulation at 36°C and postganglionic mediated contractions achieved by field-stimulation of in vitro isolated detrusor strips. With rats, pelvic nerve stimulation was carried out in vivo and postganglionic stimulation also with isolated detrusor strips. Results: All contractions were abolished by 2% lignocaine indicating they are nerve-mediated. Stimulation targets were verified with hexamethonium that completely abolished pelvic nerve responses by had no effect on detrusor strips; responses to mixed bladder wall stimulation were partially reduced. The frequency-dependence of contractile activation was similar whether by pre- or postganglionic stimulation in both pigs and rats. Sildenafil reduced contractions to preganglionic stimulation significantly more than to postganglionic stimulation. Mixed pre- and postganglionic stimulation were reduced by an intermediate extent. Conclusions: Intramural ganglia offer no frequency-dependent modulation under the experimental conditions used here and the sildenafil data are consistent with multiple sites of action underlying generation of bladder contractions. A translational aspect of these findings is discussed in terms of setting stimulation parameters for neuromodulation protocols.

      • Opportunities for microfluidic technologies in synthetic biology

        Gulati, Shelly,Rouilly, Vincent,Niu, Xize,Chappell, James,Kitney, Richard I.,Edel, Joshua B.,Freemont, Paul S.,deMello, Andrew J. The Royal Society 2009 Journal of the Royal Society, Interface Vol.6 No.suppl4

        <P>We introduce microfluidics technologies as a key foundational technology for synthetic biology experimentation. Recent advances in the field of microfluidics are reviewed and the potential of such a technological platform to support the rapid development of synthetic biology solutions is discussed.</P>

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