6emes Rencontres en Toxinologie (RT6) Societe Francaise pour 1'Etude des Toxines and Symposium with the Societe des Neurosciences

摘要

Potassium channel blockers and therapeutic application in the treatment of autoimmune neuroloical disease in rat. M. Crest, J. Devaux, R. Ben Khalifa, M. Gola, C. Beeton, E. Beraud-Juven (Laboratoire de Neurobiologie, CNRS UPR 9024, Marseille; and Laboratoire D'Immnologie, Faculte de Medecine, Marseille, France). We anticipate that blockers of the voltage-gated K channels (Kv channels) are potential candidates for the therapy of inflammatory neuropathies through their effects on #alpha#-Kv subunits expressed in lymphocytes (Kv1.3, Kv3.1) and axons (Kv1.1, Kv1.2). This hypothesis was evaluated using kaliotoxin (KTX), a scorpion toxin blocking homomeric Kv1.1, Kv1.2 and Kv1.3 channels expressed in xenope oocytes with Kd of 1 nM, 25 nM and 0.1 nM, respectively. In vitro, KTX blocks the T cells proliferation induced by antigenic stimulation with myelin basic protein (MBP) epitopes and inhibits the secretion of pro-inflammatory cytokines IL2 and TNF. In vivo, KTX reduced the clinical score of rats in which an acute experimental encephalomyelitis (EAE) was induced by injecting T cell s reactive to MBP. The nervous conduction was improved by KTX as determined from somesthesic evoked potentials. These results suggest that Kv channels blockers act in acute EAE treatment through combined neurological and immunosuppressive effects.