Toosendanin-induced inhibition of small-conductance calcium-activated potassium channels in CA1 pyramidal neurons of rat hippocampus

The effect of toosendanin (TSN) on small-conductance calcium-activated pota ssium channels (SKca) in pyramidal neurons of rat hippocampal CA1 region wa s observed using the inside-out configuration of patch-clamp technique. The results showed that TSN (1.7 similar to 170 muM) inhibited the SKca activi ty by reducing the open probability and open frequency significantly in a c oncentration-dependent manner, and the effects were partially reversible. E levating Ca2+ concentration at the intracellular side of the patch ([Ca2+]( i)) from 1 to 10 muM decreased the inhibitory efficacy. Analysis of the cha nnel kinetics indicated that TSN increased the slow closed time constant si gnificantly, while open time and unitary conductance of channel did not cha nge. These data provide a further explanation for TSN-induced facilitation of neurotransmitter release and antibotulismic effects of the drug. (C) 200 1 Elsevier Science Ireland Ltd. All rights reserved.