title: Role of membrane conductances and protein synthesis in subjective day phase advances of the hamster circadian clock by neuropeptide Y.
abstract: Neurons of the mammalian circadian pacemaker in the hypothalamic suprachiasmatic nuclei exhibit a rhythm in firing rate that can be reset by neuropeptide Y. We recorded the effects of neuropeptide Y on Na+ and K+ conductances of hamster suprachiasmatic nuclei neurons using whole-cell, perforated-patch and cell-attached patch-clamp recordings, both in dissociated and brain slice preparations. While neuropeptide Y had no effect on voltage-gated Na+ currents, neuropeptide Y activated a leak K+ current. Neuropeptide Y phase advances in the suprachiasmatic nuclei brain slice preparation were blocked by a number of K+ channel blockers (tetraethylammonium chloride, dendrotoxin-I, glybenclamide). However, a K+ ionophore, valinomycin, did not shift the rhythm. The inhibition by tetraethylammonium chloride did not persist in the presence of glutamatergic receptor blockers. We have previously shown that glutamate can oppose neuropeptide Y phase-shifting actions, suggesting that K+ channel inhibition acts by inducing glutamate release. Protein synthesis inhibitors had no effect on clock phase when applied during the subjective day, and had no influence on neuropeptide Y-induced phase shifts. On the other hand, glutamate's ability to inhibit neuropeptide Y shifts was abolished by protein synthesis inhibition. Thus, while neuropeptide Y phase shifts do not require protein synthesis, glutamate blocks neuropeptide Y shifts via increased gene expression during the subjective day, at a time when it does not reset the clock. These results indicate that neuropeptide Y phase shifts via a mechanism that does not involve changes in membrane conductance or protein synthesis.
authors.affiliation: Department of Psychology, Smith College, Northampton, MA 01063, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Hall
authors.forename: G
authors.initials: G
authors.lastname: Earle-Cruikshanks
authors.forename: M E
authors.initials: ME
authors.lastname: Harrington
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D004553:Electric Conductivity; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008647:Mesocricetus; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000166:cytology; D019789:Tetraethylammonium / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007476:Ionophores; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors; D015222:Sodium Channels; D014634:Valinomycin; D018698:Glutamic Acid; D019789:Tetraethylammonium; D000841:Anisomycin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D003513:Cycloheximide; D012964:Sodium; D011188:Potassium