Beta-agkistrodotoxin inhibits large-conductance calcium-activated potassium channels in rat hippocampal CA1 pyramidal neurons.
Effect of beta-agkistrodotoxin (beta-AgTx), a presynaptic neurotoxin purified from snake venom, on large-conductance calcium-activated potassium channels (BK(Ca)) was studied in rat hippocampal CA1 pyramidal neurons using inside-out configuration of patch-clamp technique. The results showed that in equimolar K+ (150 mM) and 1 microM intracellular Ca2+ conditions, internal application of beta-AgTx inhibited the activity of BK(Ca) by reducing open probability (P(o)) of the channels in a concentration-dependent manner. High concentration (74 nM) of beta-AgTx completely eliminated opening of the channels. However, 37 nM beta-AgTx (at -40 mV) decreased P(o) from 0.49+/-0.07 to 0.03+/-0.03, switched two open time constants (0.51+/-0.32 and 8.77+/-1.63 ms) to be a single time constant of 0.46+/-0.40 ms. The results indicate that inhibition of BK(Ca) by beta-AgTx may account for the facilitatory phase of the toxin on acetylcholine release from nerve terminals.
Wu
Ying
Y
Key Laboratory of Neurobiology, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, 200031, Shanghai, China.
Wang
Zhong-Feng
ZF
Shi
Yu-Liang
YL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D003435:Crotalid Venoms / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D003435:Crotalid Venoms; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009498:Neurotoxins; D024681:Potassium Channels, Calcium-Activated; C070121:beta-agkistrodotoxin; D011188:Potassium; D002118:Calcium