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

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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 CCKB receptor antagonist L-365,260 (1 μM). Responses to nonsulfated CCK-8 or CCK-4 were significantly weaker. Under voltage clamp (VH −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-γ-S significantly prolonged the effect of CCK-8s (n = 6), whereas GDP-β-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 CCKB receptors are prevalent in neonatal rodent spinal cord.


This article was originally published in Journal of Neurophysiology, volume 98, issue 3, in 2007. This article is available at DOI: 10.1152/jn.00148.2007

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American Physiological Society