Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine

Saïd Kourrich, Teruo Hayashi, Jian Ying Chuang, Shang Yi Tsai, Tsung Ping Su, Antonello Bonci

研究成果: 雜誌貢獻文章同行評審

142 引文 斯高帕斯(Scopus)

摘要

The sigma-1 receptor (Sig-1R), an endoplasmic reticulum (ER) chaperone protein, is an interorganelle signaling modulator that potentially plays a role in drug-seeking behaviors. However, the brain site of action and underlying cellular mechanisms remain unidentified. We found that cocaine exposure triggers a Sig-1R-dependent upregulation of D-type K+ current in the nucleus accumbens (NAc) that results in neuronal hypoactivity and thereby enhances behavioral cocaine response. Combining ex vivo and in vitro studies, we demonstrated that this neuroadaptation is caused by a persistent protein-protein association between Sig-1Rs and Kv1.2 channels, a phenomenon that is associated to a redistribution of both proteins from intracellular compartments to the plasma membrane. In conclusion, the dynamic Sig-1R-Kv1.2 complex represents a mechanism that shapes neuronal and behavioral response to cocaine. Functional consequences of Sig-1R binding to K+ channels may have implications for other chronic diseases where maladaptive intrinsic plasticity and Sig-1Rs are engaged.
原文英語
頁(從 - 到)236-247
頁數12
期刊Cell
152
發行號1-2
DOIs
出版狀態已發佈 - 一月 7 2013

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)

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