Rotenone induces KATP channel opening in PC12 cells in association with             the expression of tyrosine hydroxylase.
The activation of ATP-sensitive potassium (KATP) channels in PC12 cells             play a pivotal role in protection against the neurotoxic effect of rotenone. However,             it remains unclear why rotenone seems to preferentially affect activation of KATP             channels and if this could affect its physiological activity. In this study, we             sought to determine how the different energy states caused by various doses of             rotenone affect the KATP opening state and whether the KATP opening state influences             the expression of tyrosine hydroxylase (TH) which is related with DA synthesis.             With patch clamp technology, results showed that treatment of PC12 cells with             rotenone (0.2-1 µg/ml) for 15 min can cause KATP channel opening with significantly             increased intracellular ROS production. Treatment with rotenone (2-16 ng/ml) for             24 h also caused the channels to open with gently increased ROS. In order to study             if the rather long-term action on KATP channel opening states could affect the             specified function of PC12 cells, the KATP channel opener pinacidil and the inhibitor             glibenclamide were used to treat cells for 24 h, and the expression of TH was             detected. Our results showed that treatment of PC12 cells with glibenclamide for             24 h can notably promote TH expression and can also enhance the expression of             TH which were reduced by rotenone. These data indicate that the energy states             in PC12 induced by various doses of rotenone could significantly influence the             opening states of KATP channels. However long-term energy stress may raise the             opening rate and opening sensitivity of this channel. In addition, our results             demonstrate for the first time that activation of plasma membrane KATP channels             induced by rotenone inhibits TH expression which influences DA synthesis in PC12             cells.
Institute of Life Science, School of Public Health, Chongqing Medical University, Chongqing 400016, PR China.
Qunhua
Q
Bai
Junlin
J
He
Jingfu
J
Qiu
Yang
Y
Wang
Shibo
S
Wang
Yun
Y
Xiu
Chao
C
Yu
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D054086:KATP Channels; D017382:Reactive Oxygen Species; D012402:Rotenone; D020110:Pinacidil; D014446:Tyrosine 3-Monooxygenase; D005905:Glyburide; D004298:Dopamine