Volume 27, Issue 3 (September 2023)                   Physiol Pharmacol 2023, 27(3): 319-330 | Back to browse issues page

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Taghadosi H, Tabatabai Ghomsheh F, Farajidavar A, Khazaee F, Hoseinpour F. The effect of calcium channels blockade on slow-wave distribution in the electrophysiological model of human gastric wall smooth muscle cells. Physiol Pharmacol 2023; 27 (3) :319-330
URL: http://ppj.phypha.ir/article-1-1882-en.html
The effect of calcium channels blockade on slow-wave distribution in the electrophysiological model of human gastric wall smooth muscle cells
Hossein Taghadosi , Farhad Tabatabai Ghomsheh , Aydin Farajidavar , Faezeh Khazaee , Fatemeh Hoseinpour
Abstract:   (6676 Views)

Introduction: Two of the most important ion channels in the smooth muscle membrane are L-type and T-type calcium channels. L-type calcium channels are responsible for smooth muscle contraction, while T-type calcium channels are involved in cell membrane depolarization.
Methods: In this study, a model consisting of 1200 cells was used to simulate the smooth muscle of the gastric wall. The paper explores the effects of blocking 10%, 50%, 90%, and 100% of L-type and T-type calcium channels on the spatiotemporal wavefront propagation in human gastric wall smooth muscle cells, simulated separately.
Results: The results showed that complete blockage had the most significant effect on the slow-wave. Blockage of the L-type calcium channel led to a reduction of -3.4% and -0.8% in the membrane potential during the spike and plateau phases, respectively. The T-type calcium channel reduced the spike and resting membrane potential by -1.8% and -0.9%, respectively. In addition, the L-type calcium channel exhibited a greater impact on reducing muscle contraction compared to the T-type calcium channel. This suggests that higher blockage of calcium channels led to decreased membrane potential during slow-wave phases and reduced muscle contraction, compared to the physiological state.
Conclusion: Blocking ion channels in electrophysiological models can potentially help control gastrointestinal tract motility disorders and smooth muscle contraction.

Keywords: Stomach, Smooth Muscle Cell, Slow-wave, Calcium Channel Blockers, Electrophysiology
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Type of Manuscript: Experimental research article | Subject: Blood and Immune System
References
1. Annaházi A, Róka R, Rosztóczy A, Wittmann T. Role of antispasmodics in the treatment of irritable bowel syndrome. World J Gastoentrol: WJG 2014; 20: 6031. [DOI:10.3748/wjg.v20.i20.6031]
2. Bayginov O, Bonev A, Boev K, Papasova M. Electromechanical coupling in cat stomach smooth muscle in Ca2+-free EGTA-containing solutions. Acta Physiol Pharmacol Bulg 1989; 15: 31-38.
3. Beyder A, Farrugia G. Targeting ion channels for the treatment of gastrointestinal motility disorders. Therap Adv Gastroenterol 2012; 5: 5-21. [DOI:10.1177/1756283X11415892]
4. Blanc O. A computer model of human atrial arrhythmia (PhD thesis). Lausanne, Ecole Polytechnique (EPFL) 2002.
5. Brandstaeter S, Gizzi A, Fuchs SL, Gebauer AM, Aydin RC, Cyron CJ. Computational model of gastric motility with active-strain electromechanics. ZAMM- Z Angew Math Mech/Zeitschrift für Angewandte Mathematik und Mechanik 2018; 98: 2177-2197. [DOI:10.1002/zamm.201800166]
6. Carson DA, O’Grady G, Du P, Gharibans AA, Andrews CN. Body surface mapping of the stomach: New directions for clinically evaluating gastric electrical activity. Neurogastroenterol Motil 2021; 33: e14048. [DOI:10.1111/nmo.14048]
7. Chul Kim Y, Don Koh S, Sanders KM. Voltage-dependent inward currents of interstitial cells of Cajal from murine colon and small intestine. J physiol 2002; 541: 797-810. [DOI:10.1113/jphysiol.2002.018796]
8. Corrias A, Buist M L. Quantitative cellular description of gastric slow wave activity. American Journal of Physiology-Gastrointestinal and Liver Physiology 2008; 294: G989-G995. [DOI:10.1152/ajpgi.00528.2007]
9. Corrias A, Buist ML. A quantitative model of gastric smooth muscle cellular activation. Ann Biomed Eng 2007; 35: 1595-1607. [DOI:10.1007/s10439-007-9324-8]
10. Du P, Calder S, Angeli TR, Sathar S, Paskaranandavadivel N, O’Grady G, et al. Progress in mathematical modeling of gastrointestinal slow wave abnormalities. Front Physiol 2018; 8: 1136. [DOI:10.3389/fphys.2017.01136]
11. Du P, Liu JY, Sukasem A, Qian A, Calder S, Rudd JA. Recent progress in electrophysiology and motility mapping of the gastrointestinal tract using multi-channel devices. J R Soc N Z 2020; 50: 316-330. [DOI:10.1080/03036758.2020.1735455]
12. Evans ED, Mangel AW. Depolarization-stimulated contractility of gastrointestinal smooth muscle in calcium-free solution: a review. ISRN gastroenterol 2010; 2011. [DOI:10.5402/2011/692528]
13. Farajidavar A. Bioelectronics for mapping gut activity. Brain Res 2018; 1693: 169-173. [DOI:10.1016/j.brainres.2018.03.004]
14. Franck H, Kong I, Shuttleworth C, Sanders K. Rebound excitation and alternating slow wave patterns depend upon eicosanoid production in canine proximal colon. J physiol 1999; 520: 885. [DOI:10.1111/j.1469-7793.1999.00885.x]
15. Hedley P L, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink P A, et al. The genetic basis of long QT and short QT syndromes: a mutation update. Hum Mutat 2009; 30: 1486-1511. [DOI:10.1002/humu.21066]
16. Hocke M, Schöne U, Richert H, Görnert P, Keller J, Layer P, et al. Every slow-wave impulse is associated with motor activity of the human stomach. Am J Physiol Gastrointest Liver Physiol 2009; 296: 709-716. [DOI:10.1152/ajpgi.90318.2008]
17. Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J physiol 1952; 117: 500.
19. Hotta A, Okada N, Suzuki H. Mibefradil-sensitive component involved in the plateau potential in submucosal interstitial cells of the murine proximal colon. Biochem Biophys Res Commun 2007; 353: 170-176. [DOI:10.1016/j.bbrc.2006.12.003]
20. Huizinga J, Farraway L, Den Hertog A. Generation of slow-wave-type action potentials in canine colon smooth muscle involves a non-L-type Ca2+ conductance. The J Physiol 1991; 442: 15-29. [DOI:10.1113/jphysiol.1991.sp018779]
21. Huizinga JD. II. Gastric motility: lessons from mutant mice on slow waves and innervation. Am J Physiol Gastrointest Liver Physiol 2001; 281: 1129-1134. [DOI:10.1152/ajpgi.2001.281.5.G1129]
22. Jung KT, Park H, Kim J-H, Shin D-J, Joung B Y, Lee M-H, et al. The relationship between gastric myoelectric activity and SCN5A mutation suggesting sodium channelopathy in patients with brugada syndrome and functional dyspepsia-a pilot study. J Neurogastroenterol Motil 2012; 18: 58. [DOI:10.5056/jnm.2012.18.1.58]
23. Kushner J, Ferrer X, Marx SO. Roles and Regulation of Voltage-gated Calcium Channels in Arrhythmias. J Innov Card Rhythm Manag 2019; 10: 3874. [DOI:10.19102/icrm.2019.101006]
24. Lees-Green R, Du P, O’Grady G, Beyder A, Farrugia G, Pullan A. Biophysically based modeling of the interstitial cells of Cajal: current status and future perspectives. Front Physiol 2011; 2: 29. [DOI:10.3389/fphys.2011.00029]
25. Lin Z, Chen J. Developments in gastrointestinal electrical stimulation. Critical Reviews™ in Biomedical Engineering 2017; 45. [DOI:10.1615/CritRevBiomedEng.v45.i1-6.120]
26. Miedema BW, Sarr M, Kelly K. Pacing the human stomach. Surgery 1992; 111: 143-150.
27. Nasu T, Murase H, Shibata H. Manganese ions penetrate via L-type Ca2+ channels and induce contraction in high-K+ medium in ileal longitudinal muscle of guinea-pig. Gen Pharmacol 1995; 26: 381-386. [DOI:10.1016/0306-3623(94)00186-Q]
28. O’Grady G, Du P, Cheng LK, Egbuji JU, Lammers WJ, Windsor JA, et al. Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping. Am J Physiol Gastrointest Liver Physiol 2010; 299: G585-G592. [DOI:10.1152/ajpgi.00125.2010]
29. Poh Y C, Corrias A, Cheng N, Buist M L. A quantitative model of human jejunal smooth muscle cell electrophysiology. PLoS One 2012; 7: e42385. [DOI:10.1371/journal.pone.0042385]
30. Radulovic M, Anand P, Korsten MA, Gong B. Targeting ion channels: An important therapeutic implication in gastrointestinal dysmotility in patients with spinal cord injury. J Neurogastroenterol Motil 2015; 21: 494. [DOI:10.5056/jnm15061]
31. Rhee PL, Lee JY, Son HJ, Kim JJ, Rhee JC, Kim S, et al. Analysis of pacemaker activity in the human stomach. J physiol 2011; 589: 6105-6118. [DOI:10.1113/jphysiol.2011.217497]
32. Rychter J, Espín F, Gallego D, Vergara P, Jiménez M, Clavé P. Colonic smooth muscle cells and colonic motility patterns as a target for irritable bowel syndrome therapy: mechanisms of action of otilonium bromide. Therap Adv Gastroenterol 2014; 7: 156-166. [DOI:10.1177/1756283X14525250]
33. Sanders KM, Koh SD, Ward SM. Organization and electrophysiology of interstitial cells of Cajal and smooth muscle cells in the gastrointestinal tract. Physiology of the gastrointestinal tract: Elsevier, 2006: 533-576. [DOI:10.1016/B978-012088394-3/50023-4]
34. Seth S, Seth S. Calcium channels and calcium channel blockers. Indian J Physiol Pharmacol 1991; 35: 217-231.
35. Sha W, Pasricha PJ, Chen JD. Rhythmic and spatial abnormalities of gastric slow waves in patients with functional dyspepsia. J Clin Gastroenterol 2009; 43: 123-129. [DOI:10.1097/MCG.0b013e318157187a]
36. Shinohara Y, Kosaka I. Contribution of intracellular stored calcium to contractile activation in contractures of stomach circular muscle of Bufo vulgaris formosus. Japan J physiol 1984; 34: 443-455. [DOI:10.2170/jjphysiol.34.443]
37. Suzuki H, Hirst G. Regenerative potentials evoked in circular smooth muscle of the antral region of guinea-pig stomach. J physiol 1999; 517: 563-573. [DOI:10.1111/j.1469-7793.1999.0563t.x]
38. Taghadosi H, Ghomsheh FT, Dabanloo NJ, Farajidavar A. Electrophysiological modeling of the effect of potassium channel blockers on the distribution of stimulation wave in the human gastric wall cells. J Biomech 2021; 127: 110662. [DOI:10.1016/j.jbiomech.2021.110662]
39. Taghadosi H, Tabatabai Ghomsheh F, Farajidavar A, Khazaee F, Hoseinpour F, Beshkooh Z. Electromechanical modeling and simulation of the physiological state of human gastric wall smooth muscle cells. Comput Sci Eng 2022a; 2: 9-19. [DOI:10.5812/gct.119450]
40. Taghadosi H, Tabatabai Ghomsheh F, Jafarnia Dabanloo N, Farajidavar A. The Role of Potassium Channel Gates in the Electrophysiology of the Human Gastric Smooth Muscle Cell. 2022b; In Press: e119450. [DOI:10.5812/gct.119450]
41. To KH, Gui P, Li M, Zawieja SD, Castorena-Gonzalez JA, Davis MJ. T-type, but not L-type, voltage-gated calcium channels are dispensable for lymphatic pacemaking and spontaneous contractions. Sci Rep 2020; 10: 1-24. [DOI:10.1038/s41598-019-56953-3]
42. Van Helden DF, Laver DR, Holdsworth J, Imtiaz M S. Generation and propagation of gastric slow waves. Clin Exp Pharmacol Physiol 2010; 37: 516-524. [DOI:10.1111/j.1440-1681.2009.05331.x]
43. Ward SM, Dixon RE, De Faoite A, Sanders KM. Voltage-dependent calcium entry underlies propagation of slow waves in canine gastric antrum. J physiol 2004; 561: 793-810. [DOI:10.1113/jphysiol.2004.076067]
44. Wegener JW, Schulla V, Koller A, Klugbauer N, Feil R, Hofmann F. Control of intestinal motility by the Ca (v) 1.2 L-type calcium channel in mice. FASEB J 2006; 20: 1260-1262. [DOI:10.1096/fj.05-5292fje]
45. Whittaker DG, Clerx M, Lei CL, Christini DJ, Mirams GR. Calibration of ionic and cellular cardiac electrophysiology models. Wiley Interdiscip Rev Syst Biol Med 2020; 12: e1482. [DOI:10.1002/wsbm.1482]
46. Yeoh JW, Corrias A, Buist ML. Modelling human colonic smooth muscle cell electrophysiology. Cell Mol Bioeng 2017; 10: 186-197. [DOI:10.1007/s12195-017-0479-6]
47. Yoneda S, Takano H, Takaki M, Suzuki H. Properties of spontaneously active cells distributed in the submucosal layer of mouse proximal colon. The Journal of physiology 2002; 542: 887-897. [DOI:10.1113/jphysiol.2002.018705]
48. Zhou H, Kong D-H, Pan Q-W, Wang H-H. Sources of calcium in agonist-induced contraction of rat distal colon smooth muscle in vitro. World J Gastoentrol 2008; 14: 1077. [DOI:10.3748/wjg.14.1077]
49. Zhou J, Jameson C, Ho V. High-Amplitude Gastric Contractions following Laparoscopic Sleeve Gastrectomy. Case rep surg 2019; 2019. [DOI:10.1155/2019/7457361]
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