Patch-Clamp Study on T-Lymphocyte Potassium Conductance in Patients with Chronic Renal Failure

Teisseyre, Andrzej; Zmonarski, Stawomir C.; Klinger, Marian; Mozrzymas, Jerzy W.; Miękisz, Stanistaw

doi:10.1159/000188944

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…A patch-clamp study found an electrophysiological relevance in this context, demonstrating increased conductance of voltage-dependent K ? channels in lymphocytes of these patients [87]. The study also revealed that the activity of the channels was deeply associated with the severity of CRF.…”

Section: Effects Of Ccbs On Kv13-channel Currents and Whole-cell Memmentioning

confidence: 64%

Physiological significance of delayed rectifier K+ channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease

Kazama

2014

J Physiol Sci

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T lymphocytes predominantly express delayed rectifier K(+) channels (Kv1.3) in their plasma membranes. More than 30 years ago, patch-clamp studies revealed that the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. In addition to selective channel inhibitors that have been developed, we recently showed physiological evidence that drugs such as nonsteroidal anti-inflammatory drugs, antibiotics, and anti-hypertensives effectively suppress the channel currents in lymphocytes, and thus exert immunosuppressive effects. Using experimental animal models, previous studies revealed the pathological relevance between the expression of ion channels and the progression of renal diseases. As an extension, we recently demonstrated that the overexpression of lymphocyte Kv1.3 channels contributed to the progression of chronic kidney disease (CKD) by promoting cellular proliferation and interstitial fibrosis. Together with our in-vitro results, the studies indicated the therapeutic potency of Kv1.3-channel inhibitors in the treatment or the prevention of CKD.

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Section: Effects Of Ccbs On Kv13-channel Currents and Whole-cell Memmentioning

confidence: 64%

Physiological significance of delayed rectifier K+ channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease

Kazama

2014

J Physiol Sci

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“…Peripheral lymphocytes are activated and the serum cytokine levels are known to be elevated in patients with end-stage renal disease [ 12 – 14 ]. Based on a previous patch-clamp study [ 42 ], the conductance of voltage-dependent K + -channels in lymphocytes was increased in such patients and the activity of the channels was strongly associated with the severity of renal dysfunction. In experimental animal models of renal diseases, such as renal allograft rejection [ 10 ] and glomerulonephritis [ 9 ], immunosuppression by the blockade of lymphocyte Kv1.3-channels actually prevented or ameliorated the progression of the diseases.…”

Section: Pathological Roles Of Lymphocyte Kv13-channels In Renal mentioning

confidence: 99%

Roles of Lymphocyte Kv1.3‐Channels in the Pathogenesis of Renal Diseases and Novel Therapeutic Implications of Targeting the Channels

Kazama

2015

Mediators of Inflammation

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Delayed rectifier K+-channels (Kv1.3) are predominantly expressed in T lymphocytes. Based on patch-clamp studies, the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. Using selective channel inhibitors in experimental animal models, in vivo studies then revealed the clinically relevant relationship between the channel expression and the pathogenesis of autoimmune diseases. In renal diseases, in which “chronic inflammation” or “the overstimulation of cellular immunity” is responsible for the pathogenesis, the overexpression of Kv1.3-channels in lymphocytes promotes their cellular proliferation and thus contributes to the progression of tubulointerstitial fibrosis. We recently demonstrated that benidipine, a potent dihydropyridine calcium channel blocker, which also strongly and persistently inhibits the lymphocyte Kv1.3-channel currents, suppressed the proliferation of kidney lymphocytes and actually ameliorated the progression of renal fibrosis. Based on the recent in vitro evidence that revealed the pharmacological properties of the channels, the most recent studies have revealed novel therapeutic implications of targeting the lymphocyte Kv1.3-channels for the treatment of renal diseases.

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Influence of Specific Immunotherapy on the Activity of Human T Lymphocyte Kv1.3 Voltage-Gated Potassium Channels in Insect Venom Allergic Patients

et al. 2011

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Kv1.3 channels play an important role in T lymphocytes function. CD4(+) and CD4(+)CD25(+) T cells are two broad categories of T cells that are critically involved in the immunoresponse to allergens and that are also a major target for allergen immunotherapy. The aim of the study was to evaluate the effects of venom immunotherapy (VIT) on the activity of Kv1.3. channels on noncultured subsets: CD4(+) and CD4(+)CD25(+) T cells of insect venom allergic patients. Eleven patients with allergic reactions to bee or wasp venoms participated in the study. The patients were provided VIT according to the ultrarush protocol. CD4(+) and CD4(+)CD25(+) T cells were isolated from peripheral blood mononuclear cells of VIT-treated patients by an immunomagnetic method. We used the whole-cell patch clamp technique to investigate the whole potassium chord conductance (gK) of Kv1.3. channels in CD4(+) and CD4(+)CD25(+) T cells of venom-sensitive patients before and during the course of VIT. The conductance of Kv1.3. channels on CD4(+)CD25(+) T cells decreased during the course of VIT. On day 0 it was 0.054 ± 0.07 [nS], and on day 70 it was 0.008 ± 0.09 [nS] (P = 0.03). The observed decrease of the gK of the Kv1.3 channels in the subpopulation of activated T cells may contribute to T cell tolerance and functional unresponsiveness of these cells to allergen in the early stages of VIT.

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Patch-Clamp Study on T-Lymphocyte Potassium Conductance in Patients with Chronic Renal Failure

Cited by 3 publications

References 17 publications

Physiological significance of delayed rectifier K+ channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease

Physiological significance of delayed rectifier K+ channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease

Roles of Lymphocyte Kv1.3‐Channels in the Pathogenesis of Renal Diseases and Novel Therapeutic Implications of Targeting the Channels

Influence of Specific Immunotherapy on the Activity of Human T Lymphocyte Kv1.3 Voltage-Gated Potassium Channels in Insect Venom Allergic Patients

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