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 potassium channels (SK(Ca)) in pyramidal neurons of rat hippocampal CA1 region was observed using the inside-out configuration of patch-clamp technique. The results showed that TSN (1.7 approximately 170 microM) inhibited the SK(Ca) activity by reducing the open probability and open frequency significantly in a concentration-dependent manner, and the effects were partially reversible. Elevating Ca2+ concentration at the intracellular side of the patch ([Ca2+](i)) from 1 to 10 microM decreased the inhibitory efficacy. Analysis of the channel kinetics indicated that TSN increased the slow closed time constant significantly, while open time and unitary conductance of channel did not change. These data provide a further explanation for TSN-induced facilitation of neurotransmitter release and antibotulismic effects of the drug.
Wang
Z F
ZF
Key Laboratory of Neurobiology, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P.R., China.
Shi
Y L
YL
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014315:Triterpenes
D002118:Calcium; D004365:Drugs, Chinese Herbal; D009466:Neuromuscular Blocking Agents; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; C036454:toosendanin; D014315:Triterpenes