Ion channels and lymphocyte activation.
The ion channels expressed by T lymphocytes play key roles in the control of the membrane potential and calcium signaling, thereby affecting signal transduction pathways that lead to the activation of these cells following antigenic stimulation. Disruption of these pathways can attenuate or prevent the response of T-cells to antigenic challenge resulting in immune suppression. Studies using ion channel blockers of high affinity and specificity have shown that this interference can be achieved at the level of ion channels. Suppression of immune functions by channel blockers has been demonstrated in vitro and in vivo. New information about the molecular structure of ion channels facilitates the design of more potent and more specific inhibitors. Thus, T-cell ion channels are likely to serve as targets for immunomodulatory drugs in the near future. Here, the biophysical properties, tissue distribution, regulation of expression, molecular pharmacology and role in T-cell activation of the voltage-gated Kv1.3 and the Ca(2+)-activated IKCa1 potassium channels and those of the Ca(+) release-activated Ca(2+) (CRAC) channel are reviewed.
Panyi
György
G
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. panyi@jaguar.dote.hu
Varga
Zoltán
Z
Gáspár
Rezso
R
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000276:immunology; D015220:Calcium Channels / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology* / Q000502:physiology; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D008564:Membrane Potentials / Q000276:immunology / Q000502:physiology; D011188:Potassium / Q000502:physiology; D026902:Potassium Channel Blockers / Q000276:immunology; D015221:Potassium Channels / Q000276:immunology* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011188:Potassium; D002118:Calcium