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This Article Full Text Full Text (PDF) All Versions of this Article: 98/3/1108    most recent 00148.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Oz, M. Articles by O'Donovan, M. J. Search for Related Content PubMed PubMed Citation Articles by Oz, M. Articles by O'Donovan, M. J.

Cholecystokinin B-Type Receptors Mediate a G-Protein-Dependent Depolarizing Action of Sulphated Cholecystokinin Ocatapeptide (CCK-8s) on Rodent Neonatal Spinal Ventral Horn Neurons

¹Integrative Neuroscience Section National Institute of Drug Abuse, National Institutes of Health/Department of Health and Human Services, Intramural Research Program and ²Laboratory of Neural Control, Section on Developmental Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; and ³Neurosciences, Ottawa Health Research Institute, University of Ottawa, Ontario, Canada

Submitted 8 February 2007; accepted in final form 8 June 2007

Reports of cholecystokinin (CCK) binding and expression of CCK receptors in neonatal rodent spinal cord suggest that CCK may influence neuronal excitability. In patch-clamp recordings from 19/21 ventral horn motoneurons in neonatal (PN 5–12 days) rat spinal cord slices, we noted a slowly rising and prolonged membrane depolarization induced by bath-applied sulfated CCK octapeptide (CCK-8s; 1 µM), blockable by the CCK_B receptor antagonist L-365,260 (1 µM). Responses to nonsulfated CCK-8 or CCK-4 were significantly weaker. Under voltage clamp (V_H –65 mV), 22/24 motoneurons displayed a CCK-8s-induced tetrodotoxin-resistant inward current [peak: –136 ± 28 pA] with a similar time course, mediated via reduction in a potassium conductance. In 29/31 unidentified neurons, CCK-8s induced a significantly smaller inward current (peak: –42.8 ± 5.6 pA), and I-V plots revealed either membrane conductance decrease with net inward current reversal at 101.3 ± 4.4 mV (n = 16), membrane conductance increase with net current reversing at 36.1 ± 3.8 mV (n = 4), or parallel shift (n = 9). Intracellular GTP--S significantly prolonged the effect of CCK-8s (n = 6), whereas GDP--S significantly reduced the CCK-8s response (n = 6). Peak inward currents were significantly reduced after 5-min perfusion with N-ethylmaleimide. In isolated neonatal mouse spinal cord preparations, CCK-8s (30–300 nM) increased the amplitude and discharge of spontaneous depolarizations recorded from lumbosacral ventral roots. These observations imply functional postsynaptic G-protein-coupled CCK_B receptors are prevalent in neonatal rodent spinal cord.