Skip to main content
SpringerLink
Log in

Biophysical Processes in a Urinary Bladder Detrusor Smooth Muscle Cell during Rehabilitation Stimulation of Parasympathetic Efferents: a Simulation Study

  • Published:
Neurophysiology Aims and scope

In a computer model of an urinary bladder detrusor (UBD) smooth muscle cell (SMC), we investigated coupled changes in the membrane potential (MP), partial transmembrane currents, and intracellular calcium concentration ([Ca2 +]i), caused by parasympathetic stimulation. The respective data should help to determine the biophysical basis for the choice of parameters of medical rehabilitation electrical stimulation of the UBD. Ionotropic and metabotropic effects of such stimulation having different latency periods (LPs) were simulated by, respectively, an increase in the conductivity of purinoreceptor channels of the sarcolemma and a delayed (by 70 msec) increase in the permeability of calcium channels of the sarcoplasmic reticulum (store) sensitive to inositol triphosphate (IP3), the end-product of a chain of reactions triggered by activation of muscarinic cholinergic receptors. The modeled SMC responded to single stimulation by generation of action potential (AP) close in its parameters to those in the prototype. Application of long series of identical stimuli caused, after a transient interval, forced stationary oscillations of the MP and [Ca2 +]i. The magnitudes of the latter decreased, and the mean level increased with shortening of the interstimulus intervals (ISIs). It was found that the stimulation outcome needing prior experimental refining was determined by such parameters of the parasympathetic action as the durations of the purine and muscarinic components and the delay between these components. It has been shown that, during stimulation with ISIs shorter than the above-mentioned delay, the subsiquent stimulus activates P2X channels before expiration of the delay of the IP3-channel activation evoked by the preceding stimulus. This is actually equivalent to shortening of the interval between successive activations of P2X- and IP3-channels. Simple quantitative expressions were obtained for the parameters of stimulation; a given difference in the LPs of purine and muscarinic effects of parasympathetic stimulation allowed us to calculate the ISIs providing more efficient rehabilitation stimulation of the UBD parasympathetic nerves.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. S. M. Korogod, A. V. Kochenov, and I. A. Makedonsky, “Biophysical mechanism of parasympathetic excitation of urinary bladder smooth muscle cells: a simulation study,” Neurophysiology, 46, No. 4, 199-205 (2014).

  2. A. V. Kochenov, E. P. Poddubnaya, I. A. Makedonsky, and S. M. Korogod, “Excitability characteristics of a urinary detrusor smooth muscle cell as a basis for choosing parameters of rehabilitation electrostimulation: a simulation study,” Neurophysiology, 47, No. 2, 114-122 (2015).

  3. A. V. Kochenov, E. P. Poddubnaya, I. A. Makedonsky, and S. M. Korogod, “Biophysical processes in a urinary detrusor smooth muscle cell during rehabilitation electrostimulation: a simulation study,” Neurophysiology, 47, No. 3, 215-226 (2015).

    Article  Google Scholar 

  4. I. A. Makedonsky, “Immunohistochemical investigation of the M2 and M3 muscarinic receptors in patients with bladder exstrophy,” Eur. Urol., 4, No. 2, 182 (2004).

  5. G. Burnstock, “Purinergic signaling in the gastrointestinal tract and related organs in health and disease,” Purinerg. Signal., 10, No. 1, 3-50 (2014).

    Article  CAS  Google Scholar 

  6. K. E. Andersson and A. Arner, “Urinary bladder contraction and relaxation: physiology and pathophysiology,” Physiol. Rev., 84, No. 3, 935-986 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. F. J. Ehlert, “Contractile role of M2 and M3 muscarinic receptors in gastrointestinal, airway and urinary bladder smooth muscle,” Life Sci., 74, Nos. 2/3, 355-366 (2003).

  8. C. J. Fowler, D. Griffiths, and W. C. de Groat, “The neural control of micturition,” Nat. Rev. Neurosci., 9, No. 6, 453-466 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. G. D’Agostino, A. M. Condino, V. Calvi, et al., “Purinergic P2X3 heteroreceptors enhance parasympathetic motor drive in isolated porcine detrusor, a reliable model for development of P2X selective blockers for detrusor hyperactivity,” Pharmacol. Res., 65, No. 1, 129-136 (2012).

    Article  PubMed  Google Scholar 

  10. P. D. Anthony, W. Ford, and D. A. Cockayne, “ATP and P2X purinoceptors in urinary tract disorders,” in: Urinary Tract (Handbook Exp. Pharmacol., Vol. 202), K.-E. Andersson and M. C. Michel (eds.), Springer-Verlag, Berlin, Heidelberg (2011), pp. 375-393.

  11. M. Li, S. D. Silberberg, and K. J. Swartz, “Subtypespecific control of P2X receptor channel signaling by ATP and Mg2+,” Proc. Natl. Acad. Sci. USA, 110, No. 36, E3455-E3463 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. G. Burnstock, “Purinergic signalling in the urinary tract in health and disease,” Purinerg. Signal., 10, No. 1, 103-155 (2014).

    Article  CAS  Google Scholar 

  13. K. E. Creed, R. A. Loxleyand, and J. K. Phillips, “Functional expression of muscarinic and purinoceptors in the urinary bladder of male and female rats and guinea pigs,” J. Smooth Muscle Res., 46, No. 4, 201-215 (2010).

    Article  PubMed  Google Scholar 

  14. N. T. Carnevale and M. L. Hines, The NEURON Book, Cambridge Univ. Press, Cambridge (2006).

    Book  Google Scholar 

  15. D. B. Jaffe, B. Wang, and R. Brenner, “Shaping of action potentials by type I and type II large-conductance Ca2+-activated K+ channels,” Neuroscience, 192, 205-218 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. H. Hashitani, N. J. Bramich, and G. D. Hirst, “Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder,” J. Physiol., 524, No. 2, 565-579 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. T. J. Heppner, M. E. Werner, B. Nausch, et al., “Nerveevoked purinergic signalling suppresses action potentials, Ca2+ flashes and contractility evoked by muscarinic receptor activation in mouse urinary bladder smooth muscle,” J. Physiol., 587, No. 21, 5275-5288 (2009).

  18. J. Malysz, E. S. Rovner, and G. V. Petkov, “Single-channel biophysical and pharmacological characterizations of native human large-conductance calcium-activated potassium channels in freshly isolated detrusor smooth muscle cells,” Pflügers Arch., 465, No. 7, 965-975 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. K. A. Green, R. W. Foster, and R. C. Small, “A patchclamp study of K(+)-channel activity in bovine isolated tracheal smooth muscle cells,” Br. J. Pharmacol., 102, No. 4, 871-878 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. C. H. Fry, G. Sui, and C. Wu, “T-type Ca2+channels in non-vascular smooth muscles,” Cell Calcium, 40, No. 2, 231-239 (2006).

    Article  CAS  PubMed  Google Scholar 

  21. T. B. Bolton, “Mechanisms of action of transmitters and other substances on smooth muscle,” Physiol. Rev., 59, No. 3, 606-718 (1979).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dnipropetrovsk Division of the International Center for Molecular Physiology, National Academy of Sciences of Ukraine, Dnipro (Dnipropetrovsk), Ukraine

    A. V. Kochenov & S. M. Korogod

  2. Rudnev Dnipropetrovsk Specialized Clinical Medical Center of Mother and Child of the Dnipropetrovsk Regional Council, Dnipro (Dnipropetrovsk), Ukraine

    E. P. Poddubnaya & I. A. Makedonsky

  3. Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine, Dnipro (Dnipropetrovsk), Ukraine

    A. V. Kochenov & E. P. Poddubnaya

Authors
  1. A. V. Kochenov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. P. Poddubnaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. A. Makedonsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. M. Korogod
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. V. Kochenov.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kochenov, A.V., Poddubnaya, E.P., Makedonsky, I.A. et al. Biophysical Processes in a Urinary Bladder Detrusor Smooth Muscle Cell during Rehabilitation Stimulation of Parasympathetic Efferents: a Simulation Study. Neurophysiology 48, 156–165 (2016). https://doi.org/10.1007/s11062-016-9583-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11062-016-9583-9

Keywords

Search

Navigation