title: Physiological role of Kv1.3 channel in T lymphocyte cell investigated quantitatively by kinetic modeling.
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.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Hou
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China; School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jiuping
authors.initials: J
authors.lastname: Ding
mesh_terms: D020013:Calcium Signaling; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors / Q000502:physiology*; D008564:Membrane Potentials; D008962:Models, Theoretical; D012604:Scorpion Venoms / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D051664:Kv1.3 Potassium Channel; D012604:Scorpion Venoms