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.
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.
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.
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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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