title: Involvement of TRPC3 channels in calcium oscillations mediated by OX(1) orexin receptors.
abstract: Oscillations of intracellular Ca2+ provide a novel mechanism for sustained activation of cellular processes. Receptor-activated oscillations are mainly thought to occur through rhythmic IP3-dependent store discharge. However, as shown here in HEK293 cells 1 nM orexin-A (Ox-A) acting at OX1 receptors (OX1R) triggered oscillatory Ca2+ responses, requiring external Ca2+. These responses were attenuated by interference with TRPC3 channel (but not TRPC1/4) function using dominant negative constructs, elevated Mg2+ (a blocker of many TRP channels) or inhibition of phospholipase A2. These treatments did not affect Ca2+ oscillations elicited by high concentrations of Ox-A (100 nM) in the absence of external Ca2+. OX1R are thus able to activate TRPC(3)-channel-dependent oscillatory responses independently of store discharge.
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Kuopio, POB 1627, FI-70211 Kuopio, Finland.
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Peltonen
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Magga
authors.forename: Genevieve
authors.initials: G
authors.lastname: Bart
authors.forename: Pauli M
authors.initials: PM
authors.lastname: Turunen
authors.forename: Miia S H
authors.initials: MS
authors.lastname: Antikainen
authors.forename: Jyrki P
authors.initials: JP
authors.lastname: Kukkonen
authors.forename: Karl E
authors.initials: KE
authors.lastname: Akerman
mesh_terms: D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel