Apelin-13 enhances arcuate POMC neuron activity via inhibiting M-current

Dong Kun Lee, Jae Hoon Jeong, Seunghoon Oh, Young-Hwan Jo

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0119457
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 17 2015

Fingerprint

pro-opiomelanocortin
Pro-Opiomelanocortin
Neurons
neurons
Depolarization
Programmable logic controllers
hypothalamus
receptors
Hypothalamus
Adipose Tissue
homeostasis
Homeostasis
Single-Cell Analysis
Physiological Phenomena
Glucose
pertussis toxin
glucose
phospholipase C
Pertussis Toxin
Type C Phospholipases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Apelin-13 enhances arcuate POMC neuron activity via inhibiting M-current. / Lee, Dong Kun; Jeong, Jae Hoon; Oh, Seunghoon; Jo, Young-Hwan.

In: PLoS One, Vol. 10, No. 3, e0119457, 17.03.2015.

Research output: Contribution to journalArticle

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