Abstract
Blockade of Kv1.3 K+ channels in T cells is a promising therapeutic approach for the treatment of autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. Vm24 (α-KTx 23.1) is a novel 36-residue Kv1.3-specific peptide isolated from the venom of the scorpion Vaejovis mexicanus smithi. Vm24 inhibits Kv1.3 channels of human lymphocytes with high affinity (Kd = 2.9 pM) and exhibits >1500-fold selectivity over other ion channels assayed. It inhibits the proliferation and Ca2+ signaling of human T cells in vitro and reduces delayed-type hypersensitivity reactions in rats in vivo. Our results indicate that Vm24 has exceptional pharmacological properties that make it an excellent candidate for treatment of certain autoimmune diseases.
Footnotes
This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS073712]; the Hungarian Scientific Research Fund [Grants K 60740, NK 61412]; the Hungarian Social Renewal Operational Program [Grants TÁMOP-4.2.2-08/1/2008-0019, TÁMOP-4.2.1/B-09/1/KONV-2010-007, TÁMOP-4.2.2-A-11/1/KONV-2012-0025], General Management of Academic Personnel Matters, National Autonomous University of Mexico [Grant IN204110]; the National Council for Science and Technology of Mexico; the Hungarian Science and Technology Foundation [Grant MX-10/207], and the European Union Seventh Framework Program [Grant 246556] (to R.C.R.V.). Z.V. is a Bolyai Fellow.
Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
ABBREVIATIONS:
- TEM
- effector memory T
- [Ca2+]i
- cytosolic free Ca2+ concentration
- CFSE
- carboxyfluorescein succinimidyl ester
- FACS
- fluorescence-activated cell sorting
- RCF
- remaining current fraction
- GFP
- green fluorescent protein
- DTH
- delayed-type hypersensitivity
- PBS
- phosphate-buffered saline
- ShK
- Stichodactyla helianthus toxin
- OSK1
- Orthochirus scrobiculosus toxin 1
- BmKTx
- potassium blocking toxin from Buthus martensi
- HgTx1
- hongotoxin1
- MgTx
- margatoxin
- HsTx1
- Heterometrus spinifer toxin
- ChTx
- charybdotoxin
- mAb
- monoclonal antibody
- h
- human
- m
- mouse
- r
- rat.
- Received January 31, 2012.
- Accepted May 23, 2012.
- Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics
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