A computational model of urinary bladder smooth muscle syncytium
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Certain smooth muscles, such as the detrusor of the urinary bladder, exhibit a variety of spikes that differ markedly in their amplitudes and time courses. The origin of this diversity is poorly understood but is often attributed to the syncytial nature of smooth muscle and its distributed innervation. In order to help clarify such issues, we present here a three-dimensional electrical model of syncytial smooth muscle developed using the compartmental modeling technique, with special reference to the bladder detrusor. Values of model parameters were sourced or derived from experimental data. The model was validated against various modes of stimulation employed experimentally and the results were found to accord with both theoretical predictions and experimental observations. Model outputs also satisfied criteria characteristic of electrical syncytia such as correlation between the spatial spread and temporal decay of electrotonic potentials as well as positively skewed amplitude frequency histogram for sub-threshold potentials, and lead to interesting conclusions. Based on analysis of syncytia of different sizes, it was found that a size of 21-cube may be considered the critical minimum size for an electrically infinite syncytium. Set against experimental results, we conjecture the existence of electrically sub-infinite bundles in the detrusor. Moreover, the absence of coincident activity between closely spaced cells potentially implies, counterintuitively, highly efficient electrical coupling between such cells. The model thus provides a heuristic platform for the interpretation of electrical activity in syncytial tissues.
KeywordsElectrical Syncytium Detrusor Gap Junction Smooth Muscle Compartmental Modeling
The work was supported by grants from the Department of Biotechnology (DBT), India (BT/PR14326/Med/30/483/2010) and the UKIERI (UKUTP20110055). The authors would like to thank Michael Hines and Ted Carnevale (Yale University) for their continued expert technical support with NEURON.
The manuscript does not contain clinical studies or patient data.
Conflict of interest
The authors declare no competing financial interests.
- Beach, J.M., McGahren, E.D., Duling, B.R (1998). Capillaries and arterioles are electrically coupled in hamster cheek pouch. American Journal of Physiology-Heart and Circulatory Physiology, 275 (4), H1489—H1496.Google Scholar
- Bennett, M. (1972). Autonomic neuromuscular transmission. CUP Archive.Google Scholar
- Bennett, M., & Gibson, W (1995). On the contribution of quantal secretion from close-contact and loose-contact varicosities to the synaptic potentials in the vas deferens. Philosophical Transactions of the Royal Society of London Series B: Biological Sciences, 347 (1320), 187–204.PubMedCrossRefGoogle Scholar
- Brading, A. (1987). Physiology of bladder smooth muscle. In The Physiology of the Lower Urinary Tract (pp. 161–191). Springer, .Google Scholar
- Brading, A., & Brain, K. (2011). Ion channel modulators and urinary tract function. In Urinary Tract (pp. 375–393). Springer.Google Scholar
- Carnevale, N.T., & Hines, M.L. (2006). The NEURON book. Cambridge University Press.Google Scholar
- Carr, J.J. (1991). Designer’s Handbook Instrmtn/Contr Circuits. Academic Press.Google Scholar
- Christ, G.J., Day, N.S., Day, M., Zhao, W., Persson, K., Pandita, R.K., Andersson, K.E. (2003). Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 284 (5), R1241—R1248.PubMedGoogle Scholar
- Dayan, P., & Abbott, L.F. (2001). Theoretical neuroscience: computational and mathematical modeling of neural systems. MA: MIT press Cambridge.Google Scholar
- Goodenough, D.A. (1975). The structure and permeability of isolated hepatocyte gap junctions. In Cold Spring Harbor Symposia on Quantitative Biology (vol. 40, pp. 37–43).Google Scholar
- De Groot, J.R., Veenstra, T., Verkerk, A.O., Wilders, R., Smits, J.P., Wilms-Schopman, F.J., Wiegerinck, R.F., Bourier, J., Belterman, C.N., Coronel, R., et al (2003). Conduction slowing by the gap junctional uncoupler carbenoxolone. Cardiovascular Research, 60 (2), 288–297.PubMedCrossRefGoogle Scholar
- Jack, J.J., Noble, D., Tsien, R.W. (1975). Electric current flow in excitable cells.Google Scholar
- Johnston, D., & Wu, S. M.-S. (1995). Foundations of cellular neurophysiology.Google Scholar
- Manchanda, R. (1995). Membrane current and potential change during neurotransmission in smooth muscle. Current Science, 69 (2), 140–150.Google Scholar
- Padmakumar, M., Bhuvaneshwari, K., Manchanda, R. (2012). Classification and analysis of electrical signals in urinary bladder smooth muscle using a modified vector quantization technique. In IEEE International Conference on Signal Processing and Communications (SPCOM) (pp. 1–5).Google Scholar
- Rall, W. (1964). Theoretical significance of dendritic trees for neuronal input-output relations. Neural Theory and Modeling, 73–97.Google Scholar
- Wang, X., Maake, C., Hauri, D., H, J. (2001). Occurrence of gap junctions in the urinary bladder. European Urology, 39(5 (Suppl)), 154+.Google Scholar