title: Apelin-13 enhances arcuate POMC neuron activity via inhibiting M-current.
abstract: The hypothalamus is a key element of the neural circuits that control energy homeostasis. Specific neuronal populations within the hypothalamus are sensitive to a variety of homeostatic indicators such as circulating nutrient levels and hormones that signal circulating glucose and body fat content. Central injection of apelin secreted by adipose tissues regulates feeding and glucose homeostasis. However, the precise neuronal populations and cellular mechanisms involved in these physiological processes remain unclear. Here we examine the electrophysiological impact of apelin-13 on proopiomelanocortin (POMC) neuron activity. Approximately half of POMC neurons examined respond to apelin-13. Apelin-13 causes a dose-dependent depolarization. This effect is abolished by the apelin (APJ) receptor antagonist. POMC neurons from animals pre-treated with pertussis toxin still respond to apelin, whereas the Gβγ signaling inhibitor gallein blocks apelin-mediated depolarization. In addition, the effect of apelin is inhibited by the phospholipase C and protein kinase inhibitors. Furthermore, single-cell qPCR analysis shows that POMC neurons express the APJ receptor, PLC-β isoforms, and KCNQ subunits (2, 3 and 5) which contribute to M-type current. Apelin-13 inhibits M-current that is blocked by the KCNQ channel inhibitor. Therefore, our present data indicate that apelin activates APJ receptors, and the resultant dissociation of the Gαq heterotrimer triggers a Gβγ-dependent activation of PLC-β signaling that inhibits M-current.
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, United States of America.
authors.forename: Dong Kun
authors.initials: DK
authors.lastname: Lee
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, United States of America.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Physiology, College of Medicine, Dankook University, Cheonan City, 330-714, Republic of Korea.
authors.forename: Seunghoon
authors.initials: S
authors.lastname: Oh
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, United States of America; Department of Molecular Pharmacology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, United States of America.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Jo
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D059010:Single-Cell Analysis; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin; D037342:Pertussis Toxin; D010738:Type C Phospholipases