Cicutoxin from Cicuta virosa--a new and potent potassium channel blocker in T lymphocytes.
The effect of cicutoxin, the poisonous principle of the genus Cicuta, on K+ currents of activated T lymphocytes was investigated using the patch clamp technique. Cicutoxin produced a dose-dependent [5 x 10(-6) to 7 x 10(-5) mol/l] and completely reversible block of K+ currents with an EC50 of 1.8 x 10(-5) mol/l. A maximum block of 71% was achieved with cicutoxin at a concentration of 7 x 10(-5) mol/l. Since previous studies have shown that T lymphocyte proliferation is associated with K+ currents, the effect of cicutoxin on T lymphocyte proliferation was studied by means of 3H-thymidine uptake assays. At noncytotoxic concentrations [10(-7) to 5 x 10(-5) mol/l] cicutoxin reduced the 3H-thymidine incorporation dose-dependently. In conclusion, cicutoxin is a potent K+ current blocker which inhibits K+ channel-dependent proliferation of naive and memory T lymphocytes.
Strauss
U
U
Department of Neurology, University of Rostock, Germany.
Wittstock
U
U
Schubert
R
R
Teuscher
E
E
Jung
S
S
Mix
E
E
D000480:Alkynes; D000818:Animals; D003208:Concanavalin A; D053280:Diynes; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D015394:Molecular Structure; D010047:Ovalbumin; D018408:Patch-Clamp Techniques; D037121:Plant Lectins; D010947:Plants, Toxic; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D014118:Toxins, Biological / Q000494:pharmacology
D000480:Alkynes; D053280:Diynes; D005233:Fatty Alcohols; D037121:Plant Lectins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014118:Toxins, Biological; C098499:cicutol; D003208:Concanavalin A; C010697:cicutoxin; D010047:Ovalbumin