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.
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Abe, Y., & Tomita, T. (1968). Cable properties of smooth muscle. The Journal of Physiology, 196 (1), 87–100.
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.
Bennett, M. (1972). Autonomic neuromuscular transmission. CUP Archive.
Bennett, M. (1973). Structure and electrical properties of the autonomic neuromuscular junction. Philosophical Transactions of the Royal Society of London B, Biological Sciences, 265 (867), 25–34.
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.
Bennett, M., Gibson, W., Poznanski, R. (1993). Extracellular current flow and potential during quantal transmission from varicosities in a smooth muscle syncytium. Philosophical Transactions of the Royal Society of London Series B: Biological Sciences, 342 (1300), 89–99.
Blakeley, A., & Cunnane, T (1979). The packeted release of transmitter from the sympathetic nerves of the guinea-pig vas deferens: an electrophysiological study. The Journal of Physiology, 296 (1), 85–96.
Brading, A. (1987). Physiology of bladder smooth muscle. In The Physiology of the Lower Urinary Tract (pp. 161–191). Springer, .
Brading, A. (2006). Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function. The Journal of physiology, 570 (1), 13–22.
Brading, A., & Brain, K. (2011). Ion channel modulators and urinary tract function. In Urinary Tract (pp. 375–393). Springer.
Brading, A.F. (1997). A myogenic basis for the overactive bladder. Urology, 50 (6), 57–67.
Bramich, N.J., & Brading, A.F (1996). Electrical properties of smooth muscle in the guinea-pig urinary bladder. The Journal of Physiology, 492 (Pt 1), 185–198.
Bywater, R., & Taylor, G. (1980). The passive membrane properties and excitatory junction potentials of the guinea pig deferens. The Journal of Physiology, 300 (1), 303–316.
Carnevale, N.T., & Hines, M.L. (2006). The NEURON book. Cambridge University Press.
Carr, J.J. (1991). Designer’s Handbook Instrmtn/Contr Circuits. Academic Press.
Chapman, R., & Fry, C. (1978). An analysis of the cable properties of frog ventricular myocardium. The Journal of Physiology, 283 (1), 263–282.
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.
Crane, G.J., Hines, M.L., Neild, T.O. (2001). Simulating the spread of membrane potential changes in arteriolar networks. Microcirculation, 8(1), 33–43.
Cunnane, T., & Manchanda, R (1989). Simultaneous intracellular and focal extracellular recording of junction potentials and currents, and the time course of quantal transmitter action in rodent vas deferens. Neuroscience, 30 (3), 563–575.
Cunnane, T., & Manchanda, R. (1990). On the factors which determine the time-courses of junction potentials in the guinea-pig vas deferens. Neuroscience, 37 (2), 507–516.
Dayan, P., & Abbott, L.F. (2001). Theoretical neuroscience: computational and mathematical modeling of neural systems. MA: MIT press Cambridge.
Del Castillo, J., & Katz, B. (1956). Localization of active spots within the neuromuscular junction of the frog. The Journal of Physiology, 132 (3), 630.
Elbadawi, A., Yalla, S., Resnick, N (1993). Structural basis of geriatric voiding dysfunction. iv. bladder outlet obstruction. The Journal of Urology, 150 (5 Pt 2), 1681–1695.
Fry, C., & Wu, C. (1998). The cellular basis of bladder instability. British Journal of Urology, 81, 1–8.
Fry, C., Cooklin, M., Birns, J., Mundy, A. (1999). Measurement of intercellular electrical coupling in guinea-pig detrusor smooth muscle. The Journal of Urology, 161 (2), 660–664.
Fry, C.H., Sui, G.P., Severs, N.J., Wu, C. (2004). Spontaneous activity and electrical coupling in human detrusor smooth muscle: implications for detrusor overactivity?. Urology, 63 (3), 3–10.
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).
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.
Haefliger, J.A., Tissières, P., Tawadros, T., Formenton, A., Bény, J.L., Nicod, P., Frey, P., Meda, P. (2002). Connexins 43 and 26 are differentially increased after rat bladder outlet obstruction. Experimental Cell Research, 274 (2), 216–225.
Hashitani, H., Fukuta, H., Takano, H., Klemm, M.F., Suzuki, H. (2001). Origin and propagation of spontaneous excitation in smooth muscle of the guinea-pig urinary bladder. The Journal of Physiology, 530 (2), 273–286.
Hashitani, H., Yanai, Y., Suzuki, H. (2004). Role of interstitial cells and gap junctions in the transmission of spontaneous Ca 2+ signals in detrusor smooth muscles of the guinea-pig urinary bladder. The Journal of Physiology, 559 (2), 567– 581.
Hayase, M., Hashitani, H., Kohri, K., Suzuki, H. (2009). Role of K + channels in regulating spontaneous activity in detrusor smooth muscle in situ in the mouse bladder. The Journal of Urology, 181 (5), 2355–2365.
Hines, M. (2001). NEURON: a tool for neuroscientists. The Neuroscientist, 7 (2), 123–135.
Hines, M.L., & Carnevale, N.T. (1997). The NEURON simulation environment. Neural Computation, 9 (6), 1179–1209.
Hines, M.L., & Carnevale, N.T. (2000). Expanding NEURON’s repertoire of mechanisms with nmodl. Neural Computation, 12 (5), 995–1007.
Hodgkin, A., & Rushton, W. (1946). The electrical constants of a crustacean nerve fibre. Proceedings of the Royal Society of London Series B-Biological Sciences, 133 (873), 444–479.
Holman, M.E., Taylor, G., Tomita, T. (1977). Some properties of the smooth muscle of mouse vas deferens. The Journal of Physiology, 266 (3), 751–764.
Jack, J., & Redman, S. (1971). The propagation of transient potentials in some linear cable structures. The Journal of Physiology, 215 (2), 283–320.
Jack, J.J., Noble, D., Tsien, R.W. (1975). Electric current flow in excitable cells.
Johnston, D., & Wu, S. M.-S. (1995). Foundations of cellular neurophysiology.
Katz, B. (1948). The electrical properties of the muscle fibre membrane. Proceedings of the Royal Society of London Series B-Biological Sciences, 135 (881), 506–534.
Keener, J.P. (1991). The effects of discrete gap junction coupling on propagation in myocardium. Journal of theoretical biology, 148 (1), 49–82.
Manchanda, R. (1995). Membrane current and potential change during neurotransmission in smooth muscle. Current Science, 69 (2), 140–150.
Meng, E., Young, J.S., Brading, A.F (2008). Spontaneous activity of mouse detrusor smooth muscle and the effects of the urothelium. Neurourology and Urodynamics, 27 (1), 79–87.
Moreno, A., Saez, J., Fishman, G., Spray, D (1994). Human connexin43 gap junction channels. Regulation of unitary conductances by phosphorylation. Circulation Research, 74(6), 1050–1057.
Neuhaus, J., Wolburg, H., Hermsdorf, T., Stolzenburg, J.U., Dorschner, W. (2002). Detrusor smooth muscle cells of the guinea-pig are functionally coupled via gap junctions in situ and in cell culture. Cell and Tissue Research, 309(2), 301–311.
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).
Palani, D., Ghildyal, P., Manchanda, R. (2006). Effects of carbenoxolone on syncytial electrical properties and junction potentials of guinea-pig vas deferens. Naunyn-Schmiedeberg’s Archives of Pharmacology, 374(3), 207–214.
Petkov, G.V. (2011). Role of potassium ion channels in detrusor smooth muscle function and dysfunction. Nature Reviews Urology, 9(1), 30–40.
Purves, R. (1976). Current flow and potential in a three-dimensional syncytium. Journal of Theoretical Biology, 60(1), 147–162.
Rall, W. (1964). Theoretical significance of dendritic trees for neuronal input-output relations. Neural Theory and Modeling, 73–97.
Sourav, S., & Manchanda, R. (2000). Influence of the size of syncytial units on synaptic potentials in smooth muscle. Medical and Biological Engineering and Computing, 38(3), 356–359.
Steers, W.D., & Tuttle, J.B. (2009). Role of ion channels in bladder function and voiding disorders. Current Bladder Dysfunction Reports, 4(3), 125–131.
Stjärne, L., & Stjärne, E. (1995). Geometry, kinetics and plasticity of release and clearance of atp and noradrenaline as sympathetic cotransmitters: roles for the neurogenic contraction. Progress in Neurobiology, 47(1), 45–94.
Sui, G., Coppen, S., Dupont, E., Rothery, S., Gillespie, J., Newgreen, D., Severs, N., Fry, C. (2003). Impedance measurements and connexin expression in human detrusor muscle from stable and unstable bladders. BJU International, 92(3), 297–305.
Sui, G.P., Wu, C., Fry, C. (2001). The electrophysiological properties of cultured and freshly isolated detrusor smooth muscle cells. The Journal of Urology, 165(2), 627–632.
Tanaka, I., & Sasaki, Y. (1966). On the electrotonic spread in cardiac muscle of the mouse. The Journal of General Physiology, 49(6), 1089–1110.
Tasaki, I., & Hagiwara, S. (1957). Capacity of muscle fiber membrane. The American Journal of Physiology, 188(3), 423–429.
Tomita, T. (1966). Membrane capacity and resistance of mammalian smooth muscle. Journal of Theoretical Biology, 12(2), 216– 227.
Tomita, T. (1967). Current spread in the smooth muscle of the guinea-pig vas deferens. The Journal of Physiology, 189(1), 163–176.
Turale, N., Devulapalli, A., Manchanda, R., Moudgalya, K., Sivakumar, G (2003). Simulation framework for electrophysiological networks: effect of syncytial properties on smooth-muscle synaptic potentials. Medical and Biological Engineering and Computing, 41(5), 589–594.
Wang, X., Maake, C., Hauri, D., H, J. (2001). Occurrence of gap junctions in the urinary bladder. European Urology, 39(5 (Suppl)), 154+.
Young, J.S., Brain, K.L., Cunnane, T.C (2007). The origin of the skewed amplitude distribution of spontaneous excitatory junction potentials in poorly coupled smooth muscle cells. Neuroscience, 145(1), 153–161.
Young, J.S., Meng, E., Cunnane, T.C., Brain, K.L. (2008). Spontaneous purinergic neurotransmission in the mouse urinary bladder. The Journal of Physiology, 586(23), 5743–5755.
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.
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Appukuttan, S., Brain, K.L. & Manchanda, R. A computational model of urinary bladder smooth muscle syncytium. J Comput Neurosci 38, 167–187 (2015). https://doi.org/10.1007/s10827-014-0532-6
- Electrical Syncytium
- Gap Junction
- Smooth Muscle
- Compartmental Modeling