Nature Neuroscience 9, 31 - 40 (2005)
Published online: 27 November 2005; | doi:10.1038/nn1605
ORL1 receptor–mediated internalization of N-type calcium channelsChristophe Altier1, Houman Khosravani1, Rhian M Evans1, Shahid Hameed1, Jean B Peloquin1, Brian A Vartian1, Lina Chen1, Aaron M Beedle1, Stephen S G Ferguson2, Alexandre Mezghrani3, Stefan J Dubel3, Emmanuel Bourinet3, John E McRory1
& Gerald W Zamponi11
Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada. 2
Cell Biology Research Group, Robarts Research Institute, London, Ontario, N6A 5K8, Canada. 3
Département de Physiologie, Institut de Genomique Fonctionnelle, Centre National de la Recherche Scientifique (CNRS) UMR5203, Institut National de la Santé et de la Recherche Médicale (INSERM) U661 Universités UMI & UMII, 34094 Montpellier, France.
Correspondence should be addressed to Gerald W Zamponi zamponi@ucalgary.ca The inhibition of N-type calcium channels by opioid receptor like receptor 1 (ORL1) is a key mechanism for controlling the transmission of nociceptive signals. We recently reported that signaling complexes consisting of ORL1 receptors and N-type channels mediate a tonic inhibition of calcium entry. Here we show that prolonged ( 30 min) exposure of ORL1 receptors to their agonist nociceptin triggers an internalization of these signaling complexes into vesicular compartments. This effect is dependent on protein kinase C activation, occurs selectively for N-type channels and cannot be observed with  -opioid or angiotensin receptors. In expression systems and in rat dorsal root ganglion neurons, the nociceptin-mediated internalization of the channels is accompanied by a significant downregulation of calcium entry, which parallels the selective removal of N-type calcium channels from the plasma membrane. This may provide a new means for long-term regulation of calcium entry in the pain pathway.
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