title: Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine.
abstract: 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.
authors: Cellular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors: Saïd
authors: S
authors: Kourrich
authors: Teruo
authors: T
authors: Hayashi
authors: Jian-Ying
authors: JY
authors: Chuang
authors: Shang-Yi
authors: SY
authors: Tsai
authors: Tsung-Ping
authors: TP
authors: Su
authors: Antonello
authors: A
authors: Bonci
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior; D066298:In Vitro Techniques; D051663:Kv1.2 Potassium Channel / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D009714:Nucleus Accumbens / Q000378:metabolism*; D017480:Receptors, sigma / Q000235:genetics / Q000378:metabolism*; D000097605:Sigma-1 Receptor
chemical_list: D003042:Cocaine; D051663:Kv1.2 Potassium Channel; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor