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Physiological Role of Kv1.3 Channel in T Lymphocyte Cell Investigated Quantitatively by Kinetic Modeling

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  • Panpan Hou
  • Rong Zhang
  • Yongfeng Liu
  • Jing Feng
  • Wei Wang
  • Yingliang Wu
  • Jiuping Ding

Abstract

Kv1.3 channel is a delayed rectifier channel abundant in human T lymphocytes. Chronic inflammatory and autoimmune disorders lead to the over-expression of Kv1.3 in T cells. To quantitatively study the regulatory mechanism and physiological function of Kv1.3 in T cells, it is necessary to have a precise kinetic model of Kv1.3. In this study, we firstly established a kinetic model capable to precisely replicate all the kinetic features for Kv1.3 channels, and then constructed a T-cell model composed of ion channels including Ca2+-release activated calcium (CRAC) channel, intermediate K+ (IK) channel, TASK channel and Kv1.3 channel for quantitatively simulating the changes in membrane potentials and local Ca2+ signaling messengers during activation of T cells. Based on the experimental data from current-clamp recordings, we successfully demonstrated that Kv1.3 dominated the membrane potential of T cells to manipulate the Ca2+ influx via CRAC channel. Our results revealed that the deficient expression of Kv1.3 channel would cause the less Ca2+ signal, leading to the less efficiency in secretion. This was the first successful attempt to simulate membrane potential in non-excitable cells, which laid a solid basis for quantitatively studying the regulatory mechanism and physiological role of channels in non-excitable cells.

Suggested Citation

  • Panpan Hou & Rong Zhang & Yongfeng Liu & Jing Feng & Wei Wang & Yingliang Wu & Jiuping Ding, 2014. "Physiological Role of Kv1.3 Channel in T Lymphocyte Cell Investigated Quantitatively by Kinetic Modeling," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-9, March.
  • Handle: RePEc:plo:pone00:0089975
    DOI: 10.1371/journal.pone.0089975
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    References listed on IDEAS

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    1. Murali Prakriya & Stefan Feske & Yousang Gwack & Sonal Srikanth & Anjana Rao & Patrick G. Hogan, 2006. "Orai1 is an essential pore subunit of the CRAC channel," Nature, Nature, vol. 443(7108), pages 230-233, September.
    2. Wei Wang & Feng Xiao & Xuhui Zeng & Jing Yao & Ming Yuchi & Jiuping Ding, 2012. "Optimal Estimation of Ion-Channel Kinetics from Macroscopic Currents," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-12, April.
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