title: G-protein-gated inwardly rectifying K+ channel 4 (GIRK4) immunoreactivity in chemically defined neurons of the hypothalamic arcuate nucleus that control body weight.
abstract: G-protein-gated inwardly rectifying K(+) channels (GIRKs; also called Kir3) are a family of K(+) channels, which are activated (opened) via a signal transduction cascade starting with ligand-stimulated G-protein-coupled receptors (GPCRs). Four GIRK genes have been identified (GIRK1-4). GIRK4 (Kir3.4) has a role in regulating energy homeostasis, since mice with a targeted mutation in the GIRK4 gene exhibit a predisposition to late-onset obesity. GIRK4 mRNA is expressed in hypothalamic regions that harbor neurons involved in the regulation of food intake and body weight. Using goat and rabbit antisera to the GIRK4 protein, the cellular localization and transmitter content of GIRK4-immunoreactive neurons was determined in the hypothalamic arcuate nucleus, a region that contains neurons which are accessible to circulating hormones and is intimately associated with the control of body weight. GIRK4-immunoreactive large cell bodies were demonstrated in the ventrolateral part of the arcuate nucleus, with smaller neuronal cell bodies in the ventromedial part of the nucleus. Double-labeling showed presence of GIRK4 immunoreactivity in large neurons of the ventrolateral arcuate nucleus containing the peptides α-melanocyte-stimulating hormone (α-MSH), a marker for pro-opiomelanocortin (POMC) neurons, and cocaine- and amphetamine-regulated transcript (CART). GIRK4 immunoreactivity was also seen in neurons of the ventromedial part of the arcuate nucleus containing agouti-regulated peptide (AgRP) and neuropeptide Y (NPY). The results suggest that the GIRK4 channel protein plays a role in regulating membrane excitability in chemically defined neurons of the arcuate nucleus that control body weight.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Vaia
authors.initials: V
authors.lastname: Kloukina
authors.forename: Silke
authors.initials: S
authors.lastname: Herzer
authors.forename: Niklas
authors.initials: N
authors.lastname: Karlsson
authors.forename: Monica
authors.initials: M
authors.lastname: Perez
authors.forename: Teresa
authors.initials: T
authors.lastname: Daraio
authors.forename: Björn
authors.initials: B
authors.lastname: Meister
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology* / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology*; D003078:Colchicine / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D006041:Goats / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011817:Rabbits / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000521:alpha-MSH / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D054369:Agouti-Related Protein; D000906:Antibodies; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D003078:Colchicine