Biophysical and pharmacological aspects of K+ channels in T lymphocytes.
Voltage-gated Kv1.3 and Ca2+-activated IKCa1 K+ channels play a pivotal role in antigen-dependent activation and proliferation of lymphocytes. These channels primarily determine the membrane potential of T cells, and thus regulate the magnitude of the Ca2+ signal required for efficient gene transcription and subsequent proliferation. Although these facts are generally well described and acknowledged, some recent discoveries have motivated research in this field, which is reviewed herein along with the basic biophysical characterization of Kv1.3 and IKCa1. The discovery of T cell subset-specific expression of Kv1.3 points towards the potential therapeutic use of high affinity and high specificity Kv1.3 inhibitors as specific immunosuppressors in the management of autoimmune diseases, such as Multiple Sclerosis. In meeting the demands for an ideal immunosuppressor, several laboratories have discovered potent natural Kv1.3- specific inhibitors and engineered peptides which have a better pharmacological profile based on the biophysical characterization of the interaction surface between the channel pore and the toxins. In contrast to the generally accepted permissive role of Kv1.3 during lymphocyte activation, the discovery of the localization of Kv1.3 in the immunological synapse might open new opportunities in the regulation of T cell activation by this channel species.
Panyi
György
G
Department of Biophysics and Cell Biology, Medical and Health Science Center, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary. panyi@jaguar.dote.hu
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology; D001703:Biophysics / Q000379:methods; D017252:CD3 Complex / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D004594:Electrophysiology; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D011188:Potassium / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D013997:Time Factors
D000941:Antigens; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D010455:Peptides; D011188:Potassium; D002118:Calcium