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1

Ion channels in T cells: from molecular pharmacology to therapy

100%
Krasznai Z.
Archivum Immunologiae et Therapiae Experimentalis
|
2005
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vol. 53
|
issue 2
127-135
EN
Ion channels of a variety of cell types, such as cardiac and smooth muscle cells and neurons, serve as targets for many drugs used in therapy. T cells also express an assortment of ion channels that are in the focus of intensive research, as they may provide efficient ways to specifically manipulate T cell function and, consequently, immune responses. T cell activation relies on the operation of voltage-gated and Ca2+-activated potassium channels and Ca2+ release-activated Ca2+ channels. Many peptide toxin and small molecule blockers of these channels are known, but inhibitors of even higher affinity and selectivity would be needed for safe and effective clinical use. The recent discovery that the expression pattern of potassium channels in T cells is subset specific emphasizes the potential that these proteins have in immunomodulation. Compounds that could suppress T cells involved in autoimmunity without affecting T cells in normal immune responses would be of enormous value. In this paper the basic properties of these channels and compounds known to influence their operation are reviewed.
2

The patch-clamp technique in investigations on T lymphocyte potassium channel modulation

100%
Teisseyre A.
Postępy Higieny i Medycyny Doświadczalnej
|
2002
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vol. 56
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issue 3
393-399
EN
This review focuses on results of patch-clamp studies on modulation of T lymphocyte potassium channel activity by physiologically relevant factors. In the preface the patch-clamp technique is briefly presented and basic properties of potassium channels in T lymphocytes are characterised. The paper contains an overview of the data on modulatory effects of extracellular and intracellular pH, temperature, extracellular potassium, extracellular divalent and trivalent metal cations, channel phosphorylation processes and membrane lipid metabolities on potassium channel activity. Some still unresolved problems in that area are indicated.
3

Regulation of human T lymphocyte potassium channel function by intracellular second messengers ? role of calcium, cyclic AMP and membrane lipid metabolities

88%
Teisseyre A.
Postępy Higieny i Medycyny Doświadczalnej
|
2000
|
vol. 54
|
issue 3
381-390
EN
This review focuses on the influence of well-known intracellular second messengers on the activity of potassium channels expressed in human T lymphocytes. Basic biophysical properties of the channels are briefly presented. Available data on the regulatory role of intracellular calcium and cyclic AMP is reviewed. Finally, a possible influence of lipid compounds, especially high-density lipoproteins, lysophospholipids and sphingolipids, on the expression and activity of potassium channels in human T lymphocytes is discussed.
4

The KVLQT1 gene is not a common target for mutations in patients with various heart pathologies

88%
Moric E., Herbert E., Mazurek U., Samelska J., Cholewa K., Trusz-Gluza M., Wilczok T.
Journal of Applied Genetics
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2002
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vol. 43
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issue 2
245-254
EN
The long QT syndrome (LQTS) is a disorder of ventricular repolarization that exposes affected individuals to cardiac arrhythmias and sudden death. The first gene for LQTS has been mapped to chromosome 11 p.15.5 by genome-wide linkage analysis. This gene, originally named KVLQT1 (and later KCNQ1), is a novel potassium channel gene. Mutations in the human KVLQT1 gene, encoding the a-subunit of the KVLQT1 channel, cause the long QT syndrome. In this work, we analysed the sequence of six KVLQT1 exons in patients with various heart pathologies. We describe 6 different mSSCP patterns with no disease-related SSCP conformers in any sample. Direct sequencing of exons 2 to 7 confirmed the absence of mutations. This suggests that the analysed region of the KVLQT1 gene is not commonly involved in pathogenesis of the long QT syndrome.
5
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Reconstitution of brain mitochondria inner membrane into planar lipid bilayer

75%
Kulawiak B., Bednarczyk P.
Acta Neurobiologiae Experimentalis
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2005
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vol. 65
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issue 3
271-276
EN
Ion channels are present in the inner mitochondrial membrane. They play an important role in cellular processes. Potassium and chloride channels are involved in regulation of mitochondrial volume, membrane potential and acidification. The mitochondrial potassium channels have been suggested as triggers and end effectors in cytoprotection. In our study we measured single channel activities after reconstitution of submitochondrial particles from rat brain mitochondria into planar lipid membranes. After incorporation, two different potassium selective currents were recorded with single channel conductance from 260 to 320 pS and from 70 to 90 pS in gradient (cis/trans) 50/450 and 50/150 mM KC1 solutions, respectively. We also observed activity of the chloride ion channel. The measured single channel conductance was from 80 to 90 pS in gradient {cis/trans) 50/450 mM KC1 solution. Our results suggest that various ion channels are present in the inner mitochondrial membrane of brain mitochondria.
6
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ATP-sensitive K+ transport in adrenal chromaffin granules

75%
Szewczyk A., Lobanov N. A., Kicinska A., Wojcik G., Nalecz M. J.
Acta Neurobiologiae Experimentalis
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2001
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vol. 61
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issue 1
1-12
EN
In the present study the influx of 86Rb+, a K+ analogue, was studied in mitochondria, microsomes and chromaffin granules prepared from adrenal gland medulla. The most active electrogenic 86Rb+ transport was found in the membrane fraction identified as chromaffin granules by marker enzyme estimation. The transport was found to be sensitive to ATP, ATPS, ADP and to the triazine dyes, but not to AMP and cAMP. The inhibition induced by ATP was observed in the absence of externally added Mg2+, suggesting that a free nucleotide, rather than the ATP-Mg complex, was required for inhibition. Furthermore, the 86Rb+ influx was found to be inhibited by Mg2+ alone, but not by Ca2+ and antidiabetic sulfonylureas. The 86Rb+ influx was not stimulated by potassium channel openers. In conclusion, our results indicate that an electrogenic, ATP-sensitive potassium transport system operates in the chromaffin granule membrane.
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