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Spontaneous Rhythmic Inward Currents Recorded in Interstitial Cells of Rabbit Portal Vein

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Abstract

It is now well established that smooth muscle of the portal vein exhibits spontaneous rhythmic contraction in vitro. The present study was designed to investigate the pacemaking mechanism(s) underlying the spontaneous rhythmic contractions in the rabbit portal vein (RPV). Using whole-cell patch clamp techniques, spontaneous inward currents were recorded at −60 mV of holding potential in freshly dispersed c-Kit immunopositive interstitial cells (ICs) isolated from sections of RPV. The inward currents were abolished by caffeine, FCCP, thapsigargin, and ryanodine, but were partially inhibited by 2-APB. Both gadolinium, a non-selective cation channel inhibitor, and niflumic acid, a chloride channel blocker, inhibited the inward currents completely. Replacement of external Na+ with NMDG+ also blocked the inward currents. W-7, a calmodulin inhibitor, increased both the amplitude and frequency of the inward currents. Taken together, these results indicate that non-selective cationic channels are involved in the generation of spontaneous inward currents recorded from ICs. Intracellular calcium concentration and calmodulin regulate the spontaneous inward currents, which may account for spontaneous rhythmic contraction in the RPV, but a role of chloride channels may not be excluded in the present study.

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References

  1. Thuneberg, L. (1982). Interstitial cells of Cajal: intestinal pacemaker cells? Advances in Anatomy, Embryology and Cell Biology, 71, 1–130.

    CAS  Google Scholar 

  2. Harhun, M. I., Pucovský, V., Povstyan, O. V., Gordienko, D. V., & Bolton, T. B. (2005). Interstitial cells in the vasculature. Journal of Cellular and Molecular Medicine, 9(2), 232–243 (review).

    Article  CAS  PubMed  Google Scholar 

  3. Langton, P., Ward, S. M., Carl, A., Norell, M. A., & Sanders, K. M. (1989). Spontaneous electrical activity of interstitial cells of Cajal isolated from canine proximal colon. Proceedings of National Academy of Sciences of the United States of America, 86(18), 7280–7284.

    Article  CAS  Google Scholar 

  4. Ward, S. M., Burns, A. J., Torihashi, S., & Sanders, K. M. (1994). Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. The Journal of Physiology, 480(Pt 1), 91–97.

    CAS  PubMed  Google Scholar 

  5. Huizinga, J. D., Thuneberg, L., Klüppel, M., Malysz, J., Mikkelsen, H. B., & Bernstein, A. (1995). W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature, 373(6512), 347–349.

    Article  CAS  PubMed  Google Scholar 

  6. Thomsen, L., Robinson, T. L., Lee, J. C., Farraway, L. A., Hughes, M. J., Andrews, D. W., et al. (1998). Interstitial cells of Cajal generate a rhythmic pacemaker current. Nature Medicine, 4(7), 848–851.

    Article  CAS  PubMed  Google Scholar 

  7. Koh, S. D., Sansers, K. M., & Ward, S. M. (1998). Spontaneous electrical rhythmicity in cultured interstitial cells of Cajal from the murine small intestine. The Journal of Physiology, 513(Pt 1), 203–213.

    Article  CAS  PubMed  Google Scholar 

  8. Dickens, E. J., Hirst, G. D., & Tomita, T. (1999). Identification of rhythmically active cells in guinea-pig stomach. The Journal of Physiology, 514(Pt 2), 515–531.

    Article  CAS  PubMed  Google Scholar 

  9. Torihashi, S., Fujimoto, T., Trost, C., & Nakayama, S. (2002). Calcium oscillation linked to pacemaking of interstitial cells of Cajal. The Journal of Biological Chemistry, 277(21), 19191–19197.

    Article  CAS  PubMed  Google Scholar 

  10. Liu, H. N., Ohya, S., Furuzono, S., Wang, J., Imaizumi, Y., & Nakayama, S. (2005). Co-contribution of IP3R and Ca2+ influx pathways to pacemaker Ca2+ activity in stomach ICC. Journal of Biological Rhythms, 20(1), 15–26.

    Article  CAS  PubMed  Google Scholar 

  11. Tokutomi, N., Maeda, H., Tokutomi, Y., Sato, D., Sugita, M., Nishikawa, S., et al. (1995). Rhythmic Cl− current and physiological roles of the intestinal c-kit-positive cells. Pflugers Archiv, 431(2), 169–177.

    Article  CAS  PubMed  Google Scholar 

  12. Huizinga, J. D., Zhu, Y., Ye, J., & Molleman, A. (2002). High-conductance chloride channels generate pacemaker currents in interstitial cells of Cajal. Gastroenterology, 123(5), 1627–1636.

    Article  CAS  PubMed  Google Scholar 

  13. Koh, S. D., Jun, J. Y., Kim, T. W., & Sanders, K. M. (2002). A Ca2+-inhibited non-selective cation conductance contributes to pacemaker currents in mouse interstitial cell of Cajal. The Journal of Physiology, 540(Pt 3), 803–814.

    Article  CAS  PubMed  Google Scholar 

  14. Povstyan, O. V., Gordienko, D. V., Harhun, M. I., & Bolton, T. B. (2003). Identification of interstitial cells of Cajal in the rabbit portal vein. Cell Calcium, 33(4), 223–239.

    Article  CAS  PubMed  Google Scholar 

  15. Greenwood, I. A., & Prestwich, S. A. (2002). Characteristics of hyperpolarization-activated cation currents in portal vein smooth muscle cells. American Journal of Physiology. Cell Physiology, 282(4), 744–753.

    Google Scholar 

  16. Harhun, M. I., Gordienko, D. V., Povstyan, O. V., Moss, R. F., & Bolton, T. B. (2004). Function of interstitial cells of Cajal in the rabbit portal vein. Circulation Research, 95(6), 619–626.

    Article  CAS  PubMed  Google Scholar 

  17. Sergeant, G. P., Hollywood, M. A., McCloskey, K. D., Thornbury, K. D., & McHale, N. G. (2000). Specialised pacemaking cells in the rabbit urethra. The Journal of Physiology, 526(Pt 2), 359–366.

    Article  CAS  PubMed  Google Scholar 

  18. Holman, M. E., Kasby, C. B., Suthers, M. B., & Wilson, J. A. (1968). Some properties of the smooth muscle of rabbit portal vein. The Journal of Physiology, 196(1), 111–132.

    CAS  PubMed  Google Scholar 

  19. McCloskey, K. D., & Gurney, A. M. (2002). Kit positive cells in the guinea pig bladder. The Journal of Urology, 168(2), 832–836.

    Article  PubMed  Google Scholar 

  20. Takeda, Y., Koh, S. D., Sanders, K. M., & Ward, S. M. (2008). Differential expression of ionic conductances in interstitial cells of Cajal in the murine gastric antrum. The Journal of Physiology, 586(3), 859–873.

    Article  CAS  PubMed  Google Scholar 

  21. Sanders, K. M., Koh, S. D., & Ward, S. M. (2006). Interstitial cells of cajal as pacemakers in the gastrointestinal tract. Annual Review of Physiology, 68, 307–343.(review).

    Article  CAS  PubMed  Google Scholar 

  22. Forrest, A. S., Ördög, T., & Sanders, K. M. (2006). Neural regulation of slow-wave frequency in the murine gastric antrum. American Journal of Physiology. Gastrointestinal and Liver Physiology, 290(3), G486–G495.

    Article  CAS  PubMed  Google Scholar 

  23. Ward, S. M., & Sanders, K. M. (2006). Involvement of intramuscular interstitial cells of Cajal in neuroeffector transmission in the gastrointestinal tract. The Journal of Physiology, 576(Pt 3), 675–682.

    Article  CAS  PubMed  Google Scholar 

  24. Johnston, L., Sergeant, G. P., Hollywood, M. A., Thornbury, K. D., & McHale, N. G. (2005). Calcium oscillations in interstitial cells of the rabbit urethra. The Journal of Physiology, 565(Pt 2), 449–461.

    Article  CAS  PubMed  Google Scholar 

  25. Ward, S. M., Ördög, T., Koh, S. D., Baker, S. A., Jun, J. Y., Amberg, G., et al. (2000). Pacemaking in interstitial cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria. The Journal of Physiology, 525(Pt 2), 355–361.

    Article  CAS  PubMed  Google Scholar 

  26. Sergeant, G. P., Hollywood, M. A., McCloskey, K. D., McHale, N. G., & Thornbury, K. D. (2001). Role of IP3 in modulation of spontaneous activity in pacemaker cells of rabbit urethra. American Journal of Physiology. Cell Physiology, 280(5), 1349–1356.

    Google Scholar 

  27. Aoyama, M., Yamada, A., Wang, J., Ohya, S., Furuzono, S., Goto, T., et al. (2004). Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293 cells. Journal of Cell Science, 117(Pt 13), 2813–2825.

    Article  CAS  PubMed  Google Scholar 

  28. Liu, H. N., Ohya, S., Wang, J., Imaizumi, Y., & Nakayama, S. (2005). Involvement of ryanodine receptors in pacemaker Ca2+ oscillation in murine gastric ICC. Biochemical and Biophysical Research Communications, 328(2), 640–646.

    Article  CAS  PubMed  Google Scholar 

  29. Harhun, M., Gordienko, D., Kryshtal, D., Pucovský, V., & Bolton, T. (2006). Role of intracellular stores in the regulation of rhythmical [Ca2+]i changes in interstitial cells of Cajal from rabbit portal vein. Cell Calcium, 40(3), 287–298.

    Article  CAS  PubMed  Google Scholar 

  30. Sanders, K. M., Ördög, T., Koh, S. D., & Ward, S. M. (2000). A novel pacemaker mechanism drives gastrointestinal rhythmicity. News in Physiological Sciences, 15, 291–298.

    CAS  PubMed  Google Scholar 

  31. Tang, J., Lin, Y., Zhang, Z., Tikunova, S., Birnbaumer, L., & Zhu, M. X. (2001). Identification of common binding sites for calmodulin and inositol 1, 4, 5-trisphosphate receptors on the carboxyl termini of trp channels. The Journal of Biological Chemistry, 276(24), 21303–21310.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang, Z., Tang, J., Tikunova, S., Johnson, J. D., Chen, Z., Qin, N., et al. (2001). Activation of Trp3 by inositol 1, 4, 5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain. Proceedings of National Academy of Sciences of the United States of America, 98(6), 3168–3173.

    Article  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China, Nos. 10732070 and 10672103.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang, Shanghai, 200240, China

    Xu Huang, Zuo-Yu Wang, Yan-Fei Han, Hong-Li Lu & Wen-Xie Xu

  2. Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, P.O. Box 888, 800 Dongchuan Road, Minhang, Shanghai, 200240, China

    Dan Zhao, Ming-Liang Zhang, Zhi-Qiang Yan & Zong-Lai Jiang

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  1. Xu Huang
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Correspondence to Wen-Xie Xu or Zong-Lai Jiang.

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Huang, X., Zhao, D., Wang, ZY. et al. Spontaneous Rhythmic Inward Currents Recorded in Interstitial Cells of Rabbit Portal Vein. Cell Biochem Biophys 57, 77–85 (2010). https://doi.org/10.1007/s12013-010-9085-0

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