Journal
TOXICON
Volume 59, Issue 4, Pages 529-546Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2011.07.016
Keywords
Autoimmune; ShK; BgK; Sea anemone; Toxin; T cell; B cell; Kv1.3; KCa3.1; Potassium channel; CRAC; Multiple sclerosis; Rheumatoid arthritis; Type-1; diabetes mellitus; ShK-186; PAP-1; Psoriasis; Transplant; ShK-192
Categories
Funding
- UC Discovery [445160]
- Iacocca Foundation [485160]
- National Health and Medical Research Council of Australia
- [NIH RO1 NS48252]
- [NIH 1R43AI085691]
- [NIH RO1 GM076063]
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Electrophysiological and pharmacological studies coupled with molecular identification have revealed a unique network of ion channels-Kv1.3, KCa3.1, CRAC (Orail + Stim1), TRPM7, Cl-swen-in lymphocytes that initiates and maintains the calcium signaling cascade required for activation. The expression pattern of these channels changes during lymphocyte activation and differentiation, allowing the functional network to adapt during an immune response. The Kv1.3 channel is of interest because it plays a critical role in subsets of T and B lymphocytes implicated in autoimmune disorders. The ShK toxin from the sea anemone Stichodactyla helianthus is a potent blocker of Kv1.3. ShK-186, a synthetic analog of ShK, is being developed as a therapeutic for autoimmune diseases, and is scheduled to begin first-in-man phase-1 trials in 2011. This review describes the journey that has led to the development of ShK-186. (C) 2011 Elsevier Ltd. All rights reserved.
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