Reversal of rotenone-induced dysfunction of astrocytic connexin43 by opening mitochondrial ATP-sensitive potassium channels.
Growing evidence suggests that the astrocytic gap junctions (GJs), mainly formed by connexin 43 (Cx43), play an important role in physiological maintenance and various central nervous system (CNS) pathological conditions. However, little is known about the role of Cx43 in Parkinson's disease (PD). In this article, we report that rotenone, a classic neurotoxin for PD, could inhibit expression of astrocytic Cx43 and gap junction permeability. ATP-sensitive potassium (K(ATP)) channel openers, iptakalim (IPT) and diazoxide (DZ), exerted protective effect on rotenone-induced dysfunction of Cx43 and astrocyte apoptosis, which was reversed by selective mitochondrial K(ATP) (mitoK(ATP)) channel blocker 5-hydroxydecanoate (5-HD). Taken together, our findings reveal that rotenone-induced dysfunction of astrocytic Cx43 may be involved in the pathology of PD. Moreover, opening mitoK(ATP) channels in astrocytes can reverse rotenone-induced dysfunction of astrocytic Cx43 and therefore protect against toxicity of rotenone on astrocytes.
Zhang
Shu
S
Department of Pharmacology, Nanjing Medical University, Jiangsu, People's Republic of China.
Liang
Rui
R
Zhou
Fang
F
Huang
Xu
X
Ding
Jian-Hua
JH
Hu
Gang
G
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019610:Cytoprotection / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D015221:Potassium Channels / Q000819:agonists* / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D014475:Uncoupling Agents / Q000633:toxicity
D018031:Connexin 43; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D015221:Potassium Channels; D011437:Propylamines; D014475:Uncoupling Agents; C117780:mitochondrial K(ATP) channel; D012402:Rotenone
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