Cholecystokinin B-type receptors mediate a G-protein-dependent depolarizing action of sulphated cholecystokinin ocatapeptide (CCK-8s) on rodent neonatal spinal ventral horn neurons

Murat Oz, Keun Hang Yang, Toni S. Shippenberg, Leo P. Renaud, Michael J. O'Donovan

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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 Gprotein-coupled CCKB receptors are prevalent in neonatal rodent spinal cord.

Original languageEnglish
Pages (from-to)1108-1114
Number of pages7
JournalJournal of Neurophysiology
Volume98
Issue number3
DOIs
Publication statusPublished - Sep 2007
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Fingerprint

Dive into the research topics of 'Cholecystokinin B-type receptors mediate a G-protein-dependent depolarizing action of sulphated cholecystokinin ocatapeptide (CCK-8s) on rodent neonatal spinal ventral horn neurons'. Together they form a unique fingerprint.

Cite this