Cholecystokinin Tunes Firing of an Electrically Distinct Subset of Arcuate Nucleus Neurons by Activating A-Type Potassium Channels

Overview

Journal J Neurosci

Specialty Neurology

Date 2002 Aug 2

PMID 12151516

Citations 29

Authors

Denis Burdakov

Frances M Ashcroft

Affiliations

Soon will be listed here.

Abstract

The physiological activity of hypothalamic arcuate nucleus (ARC) neurons is critical for dynamic maintenance of body energy homeostasis, and its malfunction can result in common metabolic disorders, such as obesity. It is therefore of interest to determine which set of ion channels shapes electrical activity in the ARC. Whole-cell patch clamp of ARC neurons in mouse brain slices identified three electrophysiologically distinct types of neurons. These were distinguished by their rebound "signatures" after hyperpolarizing current injection in current clamp and by the presence of transient inward (Type-B neurons) or outward (Type-A and Type-C neurons) subthreshold voltage-gated currents in voltage-clamp recordings. In turn, the transient outward current (A-current) of Type-C neurons had a lower activation threshold and different time and voltage dependence of inactivation than that of Type-A neurons. The brain-gut peptide cholecystokinin (CCK) has long been recognized to control food intake, but how endogenous CCK modulates the activity of central appetite-regulating networks remains unresolved. Here, we show that low (picomolar) concentrations of CCK rapidly and reversibly slow the firing of ARC Type-C neurons. This effect is mediated by postsynaptic CCK-B receptors and is attributable to potentiation of the A-current. Our study thus identifies several fundamental biophysical mechanisms underlying the physiological activity of ARC neurons and suggests a novel mechanism by which endogenous CCK may control appetite.

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