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Effects of Resibufogenin and Cinobufagin on voltage-gated potassium channels in primary cultures of rat hippocampal neurons

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Indexed by:期刊论文

Date of Publication:2011-12-01

Journal:TOXICOLOGY IN VITRO

Included Journals:Scopus、SCIE、PubMed

Volume:25

Issue:8

Page Number:1644-1653

ISSN No.:0887-2333

Key Words:Resibufogenin (RBG); Cinobufagin (CBG); Delayed rectifier potassium current (I(K)); Transient potassium current (I(A)); Hippocampal neurons; Patch clamp

Abstract:Outward delayed rectifier potassium channel and outward transient potassium channel have multiple important roles in maintaining the excitability of hippocampal neurons. The present study investigated the effects of two bufadienolides, Resibufogenin (RBG) and Cinobufagin (CBG), on the outward delayed rectifier potassium current (I(K)) and outward transient potassium current (I(A)) in rat hippocampal neurons. RBG and CBG have similar structures and both were isolated from the venom gland of toad skin. RBG inhibited both I(K) and I(A), whereas CBG inhibited I(K) without noticeable effect on I(A). Moreover, at 1 mu M concentration both RBG and CBG could alter some channel kinetics and gating properties of I(K), such as steady-state activation and inactivation curves, open probability and time constants. These findings suggested that I(K) is probably a target of bufadienolides, which may explain the mechanisms of bufadienolides' pathological effects on central nervous system. (C) 2011 Elsevier Ltd. All rights reserved.

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