Details

Autor(en) / Beteiligte

• Zamponi, Gerald W
• Beedle, Aaron M
• McRory, John E
• Poirot, Olivier
• Doering, Clinton J
• Altier, Christophe
• Barrere, Christian
• Hamid, Jawed
• Nargeot, Joel
• Bourinet, Emmanuel

Titel

Agonist-independent modulation of N-type calcium channels by ORL1 receptors

Ist Teil von

• Nature neuroscience, 2004-02, Vol.7 (2), p.118-125

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2004

Link zum Volltext

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• We have investigated modulation of voltage-gated calcium channels by nociceptin (ORL1) receptors. In rat DRG neurons and in tsA-201 cells, nociceptin mediated a pronounced inhibition of N-type calcium channels, whereas other calcium channel subtypes were unaffected. In tsA-201 cells, expression of N-type channels with human ORL1 resulted in a voltage-dependent G-protein inhibition of the channel that occurred in the absence of nociceptin, the ORL1 receptor agonist. Consistent with this observation, native N-type channels of small nociceptive dorsal root ganglion (DRG) neurons also had tonic inhibition by G proteins. Biochemical characterization showed the existence of an N-type calcium channel-ORL1 receptor signaling complex, which efficiently exposes N-type channels to constitutive ORL1 receptor activity. Calcium channel activity is thus regulated by changes in ORL1 receptor expression, which provides a possible molecular mechanism for the development of tolerance to opioid receptor agonists.