Inhibition of large-conductance Ca2+-activated K+ channels in hippocampal neurons by toosendanin

The effect of toosendanin, a selective presynaptic blocker acid effective a ntibotulismic agent, on large-conductance Ca2+-activated K+ channels was st udied in inside-out patches of pyramidal neurons freshly isolated from the hippocampal CAI region of the rat. Toosendanin (1 X 10(-6) g/ml similar to 1 X 10(-4) g/ml) was found to inhibit large-conductance Ca2+-activated K- c hannels by reducing its open probability significantly in a concentration-d ependent manner. although the effective concentration of toosendanin was lo wer in a symmetrical K+ (150 mM) solution than under asymmetrical condition s (changing K- concentration in pipette solution to 5 mM). The action was p artially reversible by washing. By decreasing the slow open time constant, toosendanin shortened the open dwell time of large-conductance Ca activated Ki channels in a dose-dependent manner. A dose-dependent reduction of unit ary current amplitude of the channel was detected after toosendanin perfusi on, On elevating the intracellular free calcium concentration from 1 to 10 muM, a similar effect on large-conductance Ca2+-activared K+ channels by to osendanin was also observed, but its efficacy wan diminished. These results show that toosendanin inhibits large-conductance Ca2+-activat ed K+ channels in hippocampal neurons by reducing the open probability and unitary current amplitude of the channel. and that Ca2+ interferes with the effect. These data provide an explanation for toosendanin-induced facilita tion of neurotransmitter release and the antibotulismic effect of the drug. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.