Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis
Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evid...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.714841/full |
| _version_ | 1819101084738650112 |
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| author | Ioannis Markakis Ioannis Markakis Ioannis Charitakis Christine Beeton Christine Beeton Melpomeni Galani Elpida Repousi Elpida Repousi Stella Aggeloglou Petros P. Sfikakis Michael W. Pennington K. George Chandy K. George Chandy Cornelia Poulopoulou |
| author_facet | Ioannis Markakis Ioannis Markakis Ioannis Charitakis Christine Beeton Christine Beeton Melpomeni Galani Elpida Repousi Elpida Repousi Stella Aggeloglou Petros P. Sfikakis Michael W. Pennington K. George Chandy K. George Chandy Cornelia Poulopoulou |
| author_sort | Ioannis Markakis |
| collection | DOAJ |
| description | Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease. |
| first_indexed | 2024-12-22T01:13:03Z |
| format | Article |
| id | doaj.art-0f9684dd16cb45ed9e75cfffbfd1bd3a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T01:13:03Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-0f9684dd16cb45ed9e75cfffbfd1bd3a2022-12-21T18:43:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.714841714841Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple SclerosisIoannis Markakis0Ioannis Markakis1Ioannis Charitakis2Christine Beeton3Christine Beeton4Melpomeni Galani5Elpida Repousi6Elpida Repousi7Stella Aggeloglou8Petros P. Sfikakis9Michael W. Pennington10K. George Chandy11K. George Chandy12Cornelia Poulopoulou13National and Kapodistrian University of Athens, Medical School, Athens, GreeceDepartment of Neurology, “St. Panteleimon” General State Hospital, Nikaia, GreeceNational and Kapodistrian University of Athens, Medical School, Athens, GreeceDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, United StatesDepartment of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United StatesNational and Kapodistrian University of Athens, Medical School, Athens, GreeceNational and Kapodistrian University of Athens, Medical School, Athens, GreeceDepartment of Neurology, “St. Panteleimon” General State Hospital, Nikaia, GreeceDepartment of Neurology, “St. Panteleimon” General State Hospital, Nikaia, GreeceNational and Kapodistrian University of Athens, Medical School, Athens, GreeceAmbiopharm, Inc., North Augusta, SC, United StatesDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, United StatesLee Kong Chian School of Medicine, Nanyang Technological University, Nanyang Ave, SingaporeNational and Kapodistrian University of Athens, Medical School, Athens, GreeceVoltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease.https://www.frontiersin.org/articles/10.3389/fphar.2021.714841/fullT cellspotassium channelsKv1.3multiple sclerosispatch clampcalcium regulation |
| spellingShingle | Ioannis Markakis Ioannis Markakis Ioannis Charitakis Christine Beeton Christine Beeton Melpomeni Galani Elpida Repousi Elpida Repousi Stella Aggeloglou Petros P. Sfikakis Michael W. Pennington K. George Chandy K. George Chandy Cornelia Poulopoulou Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis Frontiers in Pharmacology T cells potassium channels Kv1.3 multiple sclerosis patch clamp calcium regulation |
| title | Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis |
| title_full | Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis |
| title_fullStr | Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis |
| title_full_unstemmed | Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis |
| title_short | Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis |
| title_sort | kv1 3 channel up regulation in peripheral blood t lymphocytes of patients with multiple sclerosis |
| topic | T cells potassium channels Kv1.3 multiple sclerosis patch clamp calcium regulation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.714841/full |
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