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 p atch clamp technique. Cicutoxin produced a dose-dependent [5 x 10(-6) -7 x 10(-5) mol/l] and completely reversible block of K+ currents with an EC(50) 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 H-3-thymidine uptake assays. At noncytotoxic conc entrations [10(-7) -5 x 10(-5) mol/l] cicutoxin reduced the H-3-thymid ine incorporation dose-dependently. In conclusion, cicutoxin is a pote nt K+ current blocker which inhibits K+ channel-dependent proliferatio n of naive and memory T lymphocytes. (C) 1996 Academic Press, Inc.