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

University of Ottawa, Ottawa, Ontario, Canada
Journal of Neurophysiology (Impact Factor: 2.89). 10/2007; 98(3):1108-14. DOI: 10.1152/jn.00148.2007
Source: PubMed


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 microM), blockable by the CCK B receptor antagonist L-365,260 (1 microM). 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-gamma-S significantly prolonged the effect of CCK-8s (n = 6), whereas GDP-beta-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.

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Available from: Murat Oz
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    • "Surprisingly, our data demonstrated that in PV+ basket cells, CCK2 signaling was not coupled to the G q/11 -PLC pathway, but instead, to a pertussis-toxin sensitive G i/o -protein pathway. While this pathway had been alluded to in earlier studies (Knapp et al., 1990; Pommier et al., 1999; Pommier et al., 2003), and recently in spinal cord motorneurons (Oz et al., 2007), it has never been identified in cortical regions. "
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    • "CCK may also play a role in normal development. In the neonatal spinal cord, CCK depolarizes motorneurons and an unidentified group of ventral horn neurons by reducing a potassium conductance through CCK2 receptors and most likely G i/o -proteins, modulating the occurrence of developmentally important spontaneous depolarizations and discharges from lumbosacral ventral roots (Oz et al., 2007). Finally, it has recently been shown that CCK-containing cells contain clusters of synaptic vesicles which are immunoreactive for estrogen receptor α, and that estrogen is able to mobilize these vesicle clusters closer to synapses (Hart et al., 2007). "
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