Ion channels in T cells: from molecular pharmacology to therapy.

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.