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 fa st focal solution exchange methods, the actions of neuropeptide Y (NPY) wer e examined in thalamic slices of postnatal(10-16 days) rats. 2. NPY activated a K+-selective current in neurons of the thalamic reticula r 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 GABA(B) receptor-induced currents, were tota lly blocked by 0.1 mM Ba2+ and showed voltage-dependent relaxation. These p roperties indicate that the NPY-sensitive K+ current is mediated by G-prote in-activated inwardly rectifying K+ (GIRK) channels. 3. In RT neurons, NPT application reversibly reduced high-voltage-activated (HVA) currents to 33 +/- 5% (n = 40) of the control level but did not affe ct 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. NPT activation of GIRK channels was mediated via NPY1, receptors, wherea s inhibition of N- and P/Q-type Ca2+ channels was mediated by NPY2 receptor s. 5. These results show that neuropeptide Y activates KS channels and simulta neously inhibits HVA Ca2+ channels via different receptor subtypes.