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This Article Full Text Full Text (PDF) All Versions of this Article: 572/2/425    most recent jphysiol.2005.104463v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deng, P.-Y. Articles by Lei, S. Search for Related Content PubMed PubMed Citation Articles by Deng, P.-Y. Articles by Lei, S. Related Collections Neuroscience

¹ Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA

Cholecystokinin (CCK) interacts with two types of G protein-coupled receptors in the brain: CCK-A and CCK-B receptors. Both CCK and CCK-B receptors are widely distributed in the hippocampal formation, but the functions of CCK there have been poorly understood. In the present study, we initially examined the effects of CCK on GABA_A receptor-mediated synaptic transmission in the hippocampal formation and then explored the underlying cellular mechanisms by focusing on the dentate gyrus region, where the highest levels of CCK-binding sites have been detected. Our results indicate that activation of CCK-B receptors initially and transiently increased spontaneous IPSC (sIPSC) frequency, followed by a persistent reduction. The effects of CCK were more evident in juvenile rats, suggesting that they are developmentally regulated. Cholecystokinin failed to modulate the miniature IPSCs recorded in the presence of TTX and the amplitude of the evoked IPSCs, but produced a transient increase followed by a reduction in action potential firing frequency recorded from GABAergic interneurons, suggesting that CCK acts by modulating the excitability of the interneurons to regulate GABA release. Cholecystokinin reduced the amplitude of the after-hyperpolarization of the action potentials, and application of paxilline or charybdotoxin considerably reduced CCK-mediated modulation of sIPSC frequency, suggesting that the effects of CCK are related to the inhibition of Ca²⁺-activated K⁺ currents (I_K(Ca)). The effects of CCK were independent of the functions of phospholipase C, intracellular Ca²⁺ release, protein kinase C or phospholipase A₂, suggesting a direct coupling between the G proteins of CCK-B receptors and I_K(Ca). Our results provide a novel mechanism underlying CCK-mediated modulation of GABA release.

(Received 25 December 2005; accepted after revision 2 February 2006; first published online 2 February 2006)
Corresponding author S. Lei: Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA. Email: slei{at}medicine.nodak.edu

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