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A computational model of large conductance voltage and calcium activated potassium channels: implications for calcium dynamics and electrophysiology in detrusor smooth muscle cells

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Abstract

The large conductance voltage and calcium activated potassium (BK) channels play a crucial role in regulating the excitability of detrusor smooth muscle, which lines the wall of the urinary bladder. These channels have been widely characterized in terms of their molecular structure, pharmacology and electrophysiology. They control the repolarising and hyperpolarising phases of the action potential, thereby regulating the firing frequency and contraction profiles of the smooth muscle. Several groups have reported varied profiles of BK currents and I-V curves under similar experimental conditions. However, no single computational model has been able to reconcile these apparent discrepancies. In view of the channels’ physiological importance, it is imperative to understand their mechanistic underpinnings so that a realistic model can be created. This paper presents a computational model of the BK channel, based on the Hodgkin-Huxley formalism, constructed by utilising three activation processes — membrane potential, calcium inflow from voltage-gated calcium channels on the membrane and calcium released from the ryanodine receptors present on the sarcoplasmic reticulum. In our model, we attribute the discrepant profiles to the underlying cytosolic calcium received by the channel during its activation. The model enables us to make heuristic predictions regarding the nature of the sub-membrane calcium dynamics underlying the BK channel’s activation. We have employed the model to reproduce various physiological characteristics of the channel and found the simulated responses to be in accordance with the experimental findings. Additionally, we have used the model to investigate the role of this channel in electrophysiological signals, such as the action potential and spontaneous transient hyperpolarisations. Furthermore, the clinical effects of BK channel openers, mallotoxin and NS19504, were simulated for the detrusor smooth muscle cells. Our findings support the proposed application of these drugs for amelioration of the condition of overactive bladder. We thus propose a physiologically realistic BK channel model which can be integrated with other biophysical mechanisms such as ion channels, pumps and exchangers to further elucidate its micro-domain interaction with the intracellular calcium environment.

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References

  • Appukuttan, S., Brain, K.L., Manchanda, R. (2015). A computational model of urinary bladder smooth muscle syncytium. Journal of Computational Neuroscience, 38(1), 167–187.

    Article  PubMed  Google Scholar 

  • Baker, D., Pryce, G., Visintin, C., Sisay, S., Bondarenko, A.I., Vanessa Ho, W.S., Jackson, S.J., Williams, T.E., Al-Izki, S., Sevastou, I., Okuyama, M., Graier, W.F., Stevenson, L.A., Tanner, C., Ross, R., Pertwee, R.G., Henstridge, C.M., Irving, A.J., Schulman, J., Powell, K., Baker, M.D., Giovannoni, G., Selwood, D.L. (2017). Big conductance calcium-activated potassium channel openers control spasticity without sedation. British Journal of Pharmacology, 174(16), 2662–2681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berridge, M.J. (2008). Smooth muscle cell calcium activation mechanisms. The Journal of Physiology, 586(21), 5047–5061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bolton, T.B., & Imaizumi, Y. (1996). Spontaneous transient outward currents in smooth muscle cells. Cell Calcium, 20(2), 141–152.

    Article  CAS  PubMed  Google Scholar 

  • Brading, A.F. (2006). Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function. The Journal of Physiology, 570(1), 13–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bygrave, F.L., & Benedetti, A. (1996). What is the concentration of calcium ions in the endoplasmic reticulum? Cell Calcium, 19(6), 547–551.

    Article  CAS  PubMed  Google Scholar 

  • Carnevale, N., & Hines, M. (2006). The NEURON book. Cambridge: Cambridge University Press.

    Book  Google Scholar 

  • Cheng, H., & Lederer, W.J. (2008). Calcium sparks. Physiological Reviews, 88(4), 1491–1545.

    Article  CAS  PubMed  Google Scholar 

  • Cox, D., Cui, J., Aldrich, R. (1997). Allosteric gating of a large conductance Ca-activated K+ channel. The Journal of General Physiology, 110(3), 257–281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox, D.H. (2014). Modeling a Ca2+ channel/BKCa channel complex at the single-complex level. Biophysical Journal, 107(12), 2797–2814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dave, V., & Manchanda, R. (2017). A computational model of the Ca2+ transients and influence of buffering in guinea pig urinary bladder smooth muscle cells. Journal of Bioinformatics and Computational Biology, 15(03), 1750011–1750027.

    Article  CAS  PubMed  Google Scholar 

  • Donahue, B.S., & Abercrombie, R.F. (1987). Free diffusion coefficient of ionic calcium in cytoplasm. Cell Calcium, 8(6), 437–448.

    Article  CAS  PubMed  Google Scholar 

  • Engbers, J.D., Zamponi, G.W., Turner, R.W. (2013). Modeling interactions between voltage-gated Ca2+ channels and KCa1. 1 channels. Channels, 7(6), 524–529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fry, C.H., & Wu, C. (1998). The cellular basis of bladder instability. British Journal of Urology, 81(1), 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Fry, C.H., Wu, C., Sui, G.P. (1998). Electrophysiological properties of the bladder. International Urogynecology Journal, 9(5), 291–298.

    Article  CAS  Google Scholar 

  • Fry, C.H., Cooklin, M., Birns, J., Mundy, A.R. (1999). Measurement of intercellular electrical coupling in guinea-pig detrusor smooth muscle. The Journal of Urology, 161(2), 660–664.

    Article  CAS  PubMed  Google Scholar 

  • Ganitkevich, V.Y., & Isenberg, G. (1991). Depolarization-mediated intracellular calcium transients in isolated smooth muscle cells of guinea-pig urinary bladder. The Journal of Physiology, 435(1), 187–205.

    Article  CAS  Google Scholar 

  • Geng, Y., & Magleby, K.L. (2015). Single-channel kinetics of BK (Slo1) channels. Frontiers in Physiology, 5 (532), 1–24.

    Google Scholar 

  • Ghatta, S., Nimmagadda, D., Xu, X., O’Rourke, S.T. (2006). Large-conductance, calcium-activated potassium channels: structural and functional implications. Pharmacology and Therapeutics, 110(1), 103–116.

    Article  CAS  PubMed  Google Scholar 

  • Guan, X., Li, Q., Yan, J. (2017). Relationship between auxiliary gamma subunits and mallotoxin on BK channel modulation. Scientific Reports, 7, 42240–42250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta, S., & Manchanda, R. (2014). A TANH spline interpolation technique for modelling ion channels: application to BK channels in smooth muscle. International Journal of Simulation–Systems, Science &, Technology, 15 (6), 97–109.

    Google Scholar 

  • Gupta, S., & Manchanda, R. (2016). Computational model of SK channel with reference to calcium dynamics in bladder smooth muscles. In Proceedings of the 12th IASTED international conference biomedical engineering (BioMed 2016) (pp. 53–59).

  • Gupta, S., & Manchanda, R. (2018). Effect of gating charges on mediating the dual activation of BK channels in smooth muscle cells: a computational study. In: Conference proceedings: 40th annual international conference of the IEEE engineering in medicine and biology society (pp. 5838–5841). IEEE Engineering in Medicine and Biology Society.

  • Hashitani, H., & Brading, A.F. (2003). Electrical properties of detrusor smooth muscles from the pig and human urinary bladder. British Journal of Pharmacology, 140(1), 146–158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hashitani, H., Brading, A.F., Suzuki, H. (2004). Correlation between spontaneous electrical, calcium and mechanical activity in detrusor smooth muscle of the guinea-pig bladder. British Journal of Pharmacology, 141(1), 183–193.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Heppner, T., & Bonev, A. (1997). Ca(2+)-activated K+ channels regulate action potential repolarization in urinary bladder smooth muscle. American Journal of Physiology-Cell Physiology, 273(1), C110–C117.

    Article  CAS  Google Scholar 

  • Herrera, G.M., & Nelson, M.T. (2002). Differential regulation of SK and BK channels by Ca2+ signals from Ca2+ channels and ryanodine receptors in guinea-pig urinary bladder myocytes. The Journal of Physiology, 541(2), 483–492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herrera, G.M., Heppner, T.J., Nelson, M.T. (2001). Voltage dependence of the coupling of Ca(2+) sparks to BK(Ca) channels in urinary bladder smooth muscle. American Journal of Physiology Cell Physiology, 280(3), C481–90.

    Article  CAS  PubMed  Google Scholar 

  • Hirano, M., Imaizumi, Y., Muraki, K., Yamada, A., Watanabe, M. (1998). Effects of ruthenium red on membrane ionic currents in urinary bladder smooth muscle cells of the guinea-pig. Pflugers Archiv, 435(5), 645–653.

    Article  CAS  PubMed  Google Scholar 

  • Hollywood, M.A., McCloskey, K.D., McHale, N.G., Thornbury, K.D. (2000). Characterization of outward K(+) currents in isolated smooth muscle cells from sheep urethra. American Journal of Physiology-Cell Physiology, 279(2), C420–C428.

    Article  CAS  PubMed  Google Scholar 

  • Houamed, K.M., Sweet, I.R., Satin, L.S. (2010). BK Channels mediate a novel ionic mechanism that regulates glucose-dependent electrical activity and insulin secretion in mouse pancreatic β-cells. The Journal of Physiology, 588(18), 3511–3523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hristov, K.L., Chen, M., Kellett, W.F., Rovner, E.S., Petkov, G.V. (2011). Large-conductance voltage- and Ca2+-activated K+ channels regulate human detrusor smooth muscle function. American Journal of Physiology-Cell Physiology, 301(4), C903–C912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaggar, J.H., Porter, V.A., Lederer, W.J., Nelson, M.T. (2000). Calcium sparks in smooth muscle. American Journal of Physiology-Cell Physiology, 278(2), C235–C256.

    Article  CAS  PubMed  Google Scholar 

  • Kaczorowski, G.J., & Garcia, M.L. (1999). Pharmacology of voltage-gated and calcium-activated potassium channels. Current Opinion in Chemical Biology, 3(4), 448–458.

    Article  CAS  PubMed  Google Scholar 

  • Klöckner, U., & Isenberg, G. (1985). Action potentials and net membrane currents of isolated smooth muscle cells (urinary bladder of the guinea-pig). Pflügers Archiv European Journal of Physiology, 405(4), 329–339.

    Article  PubMed  Google Scholar 

  • Kobayter, S., Young, J.S., Brain, K.L. (2012). Prostaglandin E2 induces spontaneous rhythmic activity in mouse urinary bladder independently of efferent nerves. British Journal of Pharmacology, 165(2), 401–413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kochenov, A.V., Poddubnaya, E.P., Makedonsky, I.A., Korogod, S.M. (2015). Biophysical processes in a urinary bladder detrusor smooth muscle cell during rehabilitation electrostimulation: a simulation study. Neurophysiology, 47(3), 174–184.

    Article  CAS  Google Scholar 

  • Korogod, S., Kochenov, A., Makedonsky, I. (2014). Biophysical mechanism of parasympathetic excitation of urinary bladder smooth muscle cells: a simulation study. Neurophysiology, 46(4), 293–299.

    Article  CAS  Google Scholar 

  • Kyle, B.D., Bradley, E., Large, R., Sergeant, G.P., McHale, N.G., Thornbury, K.D., Hollywood, M.A. (2013). Mechanisms underlying activation of transient BK current in rabbit urethral smooth muscle cells and its modulation by IP3-generating agonists. American Journal of Physiology-Cell Physiology, 305(6), C609–C622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laver, D.R., & Lamb, G.D. (1998). Inactivation of Ca2+ release channels (ryanodine receptors RyR1 and RyR2) with rapid steps in [Ca2+] and voltage. Biophysical Journal, 74(5), 2352–2364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, U.S., & Cui, J. (2010). BK channel activation: Structural and functional insights. Trends in Neurosciences, 33(9), 415–423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lifshitz, L.M., Carmichael, J.D., Lai, F.A., Sorrentino, V., Bellvé, K., Fogarty, K.E., ZhuGe, R. (2011). Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca2+ sparks in airway myocytes. The Journal of General Physiology, 138(2), 195–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lovell, P.V., James, D.G., McCobb, D.P. (2000). Bovine versus rat adrenal chromaffin cells: big differences in BK potassium channel properties. Journal of Neurophysiology, 83(6), 3277–3286.

    Article  CAS  PubMed  Google Scholar 

  • Luo, C.-H., & Rudy, Y. (1994). A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circulation Research, 74(6), 1071–1096.

    Article  CAS  PubMed  Google Scholar 

  • Magleby, K.L. (2003). Gating mechanism of BK (Slo1) channels: so near, yet so far. The Journal of General Physiology, 121(2), 81–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahapatra, C., Brain, K., Manchanda, R. (2018a). Computational study of Hodgkin-Huxley type calcium-dependent potassium current in urinary bladder over activity. In: 2018 IEEE 8th international conference on computational advances in bio and medical sciences (ICCABS) (pp. 1–4). IEEE.

  • Mahapatra, C., Brain, K.L., Manchanda, R. (2018b). A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle. PloS One, 13(7), e0200712.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maioli, E., Greci, L., Soucek, K., Hyzdalova, M., Pecorelli, A., Fortino, V., Valacchi, G. (2009). Rottlerin inhibits ROS formation and prevents NFκ B activation in MCF-7 and HT-29 cells. Journal of Biomedicine and Biotechnology, 2009, 1–7.

    Article  CAS  Google Scholar 

  • Mandge, D., & Manchanda, R. (2018). A biophysically detailed computational model of bladder small DRG neuron soma. PLoS Computational Biology, 14(7), e1006293.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Marx, S.O., & Zakharov, S.I. (2004). Use of rottlerin and its derivatives as activators of BK channel for therapy of hypertension and related disorders. https://patents.google.com/patent/WO2006060196A2/en.

  • MATLAB. (2018). R2018a. The MathWorks Inc., Natick, Massachusetts.

  • McDougal, R.A., Morse, T.M., Carnevale, T., Marenco, L., Wang, R., Migliore, M., Miller, P.L., Shepherd, G.M., Hines, M.L. (2017). Twenty years of ModelDB and beyond: building essential modeling tools for the future of neuroscience. Journal of Computational Neuroscience, 42(1), 1–10.

    Article  PubMed  Google Scholar 

  • Meech, R.W., & Standen, N.B. (1975). Potassium activation in Helix Aspersa neurones under voltage clamp: a component mediated by calcium influx. The Journal of Physiology, 249(2), 211–259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng, E. (2009). Recent research advances in the pathophysiology of overactive bladder. Incont Pelvic Floor Dysfunct, 3(Suppl 1), 5–7.

    Google Scholar 

  • Meredith, A.L., Thorneloe, K.S., Werner, M.E., Nelson, M.T., Aldrich, R.W. (2004). Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel. Journal of Biological Chemistry, 279(35), 36746–36752.

    Article  CAS  PubMed  Google Scholar 

  • Mijailovich, S.M., Nedic, D., Svicevic, M., Stojanovic, B., Walklate, J., Ujfalusi, Z., Geeves, M.A. (2017). Modeling the actin myosin ATPase cross-bridge cycle for skeletal and cardiac muscle myosin isoforms. Biophysical Journal, 112(5), 984–996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moczydlowski, E., & Latorre, R. (1983). Gating kinetics of Ca2+-activated K+ channels from rat muscle incorporated into planar lipid bilayers. Evidence for two voltage-dependent Ca2+ binding reactions. The Journal of General Physiology, 82(4), 511–542.

    Article  CAS  PubMed  Google Scholar 

  • Nausch, B., Rode, F., Jorgensen, S., Nardi, A., Korsgaard, M.P.G., Hougaard, C., Bonev, A.D., Brown, W.D., Dyhring, T., Strobaek, D., Olesen, S.-P., Christophersen, P., Grunnet, M., Nelson, M.T., Ronn, L.C.B. (2014). NS19504: A novel BK channel activator with relaxing effect on bladder smooth muscle spontaneous phasic contractions. Journal of Pharmacology and Experimental Therapeutics, 350(3), 520–530.

    Article  PubMed  CAS  Google Scholar 

  • Orio, P., Yolima, T., Patricio, R., Carvacho, I., Garcia, M.L., Toro, L., Valverde, M.A., Latorre, R. (2006). Structural determinants for functional coupling between the β and α subunits in the Ca2+-activated K+ (BK) channel. The Journal of General Physiology, 127(2), 191–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parajuli, S.P., Hristov, K.L., Cheng, Q., Malysz, J., Rovner, E.S., Petkov, G.V. (2015). Functional link between muscarinic receptors and large-conductance Ca2+-activated K+ channels in freshly-isolated human detrusor smooth muscle cells. Pflügers Archiv-European Journal of Physiology, 467(4), 665–675.

    Article  CAS  PubMed  Google Scholar 

  • Parajuli, S.P., Zheng, Y.-M., Levin, R., Wang, Y.-X. (2016). Big-conductance Ca2+-activated K+ channels in physiological and pathophysiological urinary bladder smooth muscle cells. Channels, 10(5), 355–364.

    Article  PubMed  PubMed Central  Google Scholar 

  • Petkov, G.V. (2012). Role of potassium ion channels in detrusor smooth muscle function and dysfunction. Nature Reviews Urology, 9(1), 30–40.

    Article  CAS  Google Scholar 

  • Petkov, G.V. (2014). Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 307(6), R571–R584.

    Article  CAS  Google Scholar 

  • Petkov, G.V., & Nelson, M.T. (2005). Differential regulation of Ca2+-activated K+ channels by β-adrenoceptors in guinea pig urinary bladder smooth muscle. American Journal of Physiology-Cell Physiology, 288(6), C1255–C1263.

    Article  CAS  PubMed  Google Scholar 

  • Prosser, C.L. (1974). Smooth muscle. Annual Review of Physiology, 36(1), 503–535.

  • Rothberg, B.S., & Magleby, K.L. (2000). Voltage and Ca2+ activation of single large-conductance Ca2+-activated K+ channels described by a two-tiered allosteric gating mechanism. The Journal of General Physiology, 116(1), 75–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salkoff, L., Butler, A., Ferreira, G., Santi, C., Wei, A. (2006). High-conductance potassium channels of the SLO family. Nature Reviews Neuroscience, 7(12), 921–931.

    Article  CAS  PubMed  Google Scholar 

  • Spiess, A.-N., & Neumeyer, N. (2010). An evaluation of R 2 as an inadequate measure for nonlinear models in pharmacological and biochemical research: A Monte Carlo approach. BMC Pharmacology, 10(6), 1–11.

    Google Scholar 

  • Steephen, J.E., & Manchanda, R. (2009). Differences in biophysical properties of nucleus accumbens medium spiny neurons emerging from inactivation of inward rectifying potassium currents. Journal of Computational Neuroscience, 27(3), 453–470.

    Article  PubMed  Google Scholar 

  • Sui, G.P., Wu, C., Fry, C.H. (2001). The electrophysiological properties of cultured and freshly isolated detrusor smooth muscle cells. The Journal of Urology, 165(2), 627–632.

    Article  CAS  PubMed  Google Scholar 

  • Sun, P., Zhang, Q., Zhang, Y., Wang, F., Wang, L., Yamamoto, R., Sugai, T., Kato, N. (2015). Fear conditioning suppresses large-conductance calcium-activated potassium channels in lateral amygdala neurons. Physiology and Behavior, 138, 279–284.

    Article  CAS  PubMed  Google Scholar 

  • Tong, W.C., Choi, C.Y., Kharche, S., Holden, A.V., Zhang, H., Taggart, M.J. (2011). A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle. PloS One, 6(4), e18685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turner, W.H., & Brading, A.F. (1997). Smooth muscle of the bladder in the normal and the diseased state: pathophysiology, diagnosis and treatment. Pharmacology and Therapeutics, 75(2), 77–110.

    Article  CAS  PubMed  Google Scholar 

  • Van Goor, F., Zivadinovic, D., Stojilkovic, S.S. (2001). Differential expression of ionic channels in rat anterior pituitary cells. Molecular Endocrinology, 15(7), 1222–1236.

    Article  PubMed  Google Scholar 

  • Vergara, C., Latorre, R., Marrion, N.V., Adelman, J.P. (1998). Calcium-activated potassium channels. Current Opinion in Neurobiology, 8(3), 321–329.

    Article  CAS  PubMed  Google Scholar 

  • Zakharov, S.I., Morrow, J.P., Liu, G., Yang, L., Marx, S.O. (2005). Activation of the BK (SLO1) potassium channel by mallotoxin. Journal of Biological Chemistry, 280(35), 30882–30887.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Department of Biotechnology (DBT), India (Project No. BT/PR12973/MED/122/47/ 2016). The authors would like to thank Dr. Vijay Kumar Dave (Government Engineering College, Gandhinagar, India) for providing the complete DSM-specific Calcium Dynamics model.

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  1. Computational NeuroPhysiology Lab, Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai, 400076, India

    Suranjana Gupta & Rohit Manchanda

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Gupta, S., Manchanda, R. A computational model of large conductance voltage and calcium activated potassium channels: implications for calcium dynamics and electrophysiology in detrusor smooth muscle cells. J Comput Neurosci 46, 233–256 (2019). https://doi.org/10.1007/s10827-019-00713-9

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