Neuropeptide Y receptors differentially modulate G-protein-activated inwardly rectifying K+ channels and high-voltage-activated Ca2+ channels in rat thalamic neurons.
1. Using whole-cell patch-clamp recordings, infrared videomicroscopy and fast focal solution exchange methods, the actions of neuropeptide Y (NPY) were examined in thalamic slices of postnatal (10-16 days) rats. 2. NPY activated a K+-selective current in neurons of the thalamic reticular nucleus (RT; 20/29 neurons) and ventral basal complex (VB; 19/25 neurons). The currents in both nuclei had activation and deactivation kinetics that were very similar to those of GABAB receptor-induced currents, were totally blocked by 0.1 mM Ba2+ and showed voltage-dependent relaxation. These properties indicate that the NPY-sensitive K+ current is mediated by G-protein-activated, inwardly rectifying K+ (GIRK) channels. 3. In RT neurons, NPY application reversibly reduced high-voltage-activated (HVA) currents to 33 +/- 5 % (n = 40) of the control level but did not affect the T-type currents. Inhibition of Ca2+ currents was voltage independent and was largely mediated by effects on N- and P/Q-type channels. 4. NPY activation of GIRK channels was mediated via NPY1 receptors, whereas inhibition of N- and P/Q-type Ca2+ channels was mediated by NPY2 receptors. 5. These results show that neuropeptide Y activates K+ channels and simultaneously inhibits HVA Ca2+ channels via different receptor subtypes.
Sun
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QQ
Department of Neurology and Neurological Science, Stanford University School of Medicine, CA 94305, USA.
Huguenard
J R
JR
Prince
D A
DA
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017476:Receptors, Neuropeptide Y; D001464:Barium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins