Publication Date
1-1-2021
Journal
Frontiers in Pharmacology
DOI
10.3389/fphar.2021.714841
PMID
34630091
PMCID
PMC8495199
PubMedCentral® Posted Date
9-23-2021
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
T cells, potassium channels, Kv1.3, multiple sclerosis, patch clamp, calcium regulation
Abstract
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.
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Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Integrative Medicine Commons, Medical Sciences Commons
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