Reversal of Rotenone-Induced Dysfunction of Astrocytic Connexin43 by Opening Mitochondrial ATP-Sensitive Potassium Channels

被引：21

作者：

Zhang, Shu ^{[1
,2
]}

Liang, Rui ^{[1
]}

Zhou, Fang ^{[1
]}

Huang, Xu ^{[1
]}

Ding, Jian-Hua ^{[1
]}

Hu, Gang ^{[1
]}

机构：

[1] Nanjing Med Univ, Dept Pharmacol, Jiangsu Key Lab Neurodegenerat, Nanjing 210029, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Affiliated Hosp 1, Clin Res Ctr, Nanjing 210029, Jiangsu, Peoples R China

来源：

CELLULAR AND MOLECULAR NEUROBIOLOGY | 2011年 / 31卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Rotenone; Connexin; 43; Astrocyte; ATP-sensitive potassium channel; Iptakalim; GAP-JUNCTION CHANNELS; INDUCED CELL-DEATH; PARKINSONS-DISEASE; NEUROLOGICAL DISORDERS; DOPAMINERGIC-NEURONS; IPTAKALIM; RATS; HEMICHANNELS; APOPTOSIS; OPENER;

D O I：

10.1007/s10571-010-9560-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：111 / 117

页数：7

共 49 条

[1] Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats [J].