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Cited by 270

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Kisspeptin Excites Gonadotropin-Releasing Hormone Neurons through a Phospholipase C/Calcium-Dependent Pathway Regulating Multiple Ion Channels

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Liu, Xinhuai, Lee, Kiho, Herbison, Allan E.·2008·Endocrinology
DOI 10.1210/en.2008-0321
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Abstract

The present study used perforated-patch electrophysiology and calcium imaging in GnRH transgenic mouse lines to determine the mechanisms underlying the potent excitatory effects of kisspeptin upon GnRH neurons in the acute brain slice preparation. Kisspeptin (100 nm) depolarized (6 ± 1 mV) and/or evoked an 87 ± 4% increase in firing rate of 75% of adult GnRH neurons (n = 51). No sex differences were found. Analyses of input resistance and current-voltage curves indicated that a heterogeneous closure of potassium channels and opening of nonselective cation (NSC) channels was involved in kisspeptin’s depolarizing response. Pharmacological pretreatment with either barium, a potassium channel blocker, or flufenamic acid, an NSC channel antagonist, reduced the percentage of responding GnRH neurons from 75 to 40% (P < 0.05). Pretreatment with both barium and flufenamic acid reduced the response rate to 17% (P < 0.05). To examine the intracellular signaling cascade involved, GnRH neurons were treated with antagonists of phospholipase C (PLC), inositol-trisphosphate receptors (IP3R), and ERK1/2 before kisspeptin exposure. PLC and IP3R antagonism reduced the percentage of responding GnRH neurons from 80 to 15 and 7%, respectively (P < 0.001). Real-time calcium imaging showed that kisspeptin evoked an approximately 10% increase in intracellular calcium levels in GnRH neurons that was followed by a decrease and return to pretest calcium levels. Additional experiments indicated that mechanisms intrinsic to the GnRH neuron are responsible for their prolonged depolarizing response to kisspeptin. These studies indicate that kisspeptin activates G protein-coupled receptor 54 (GPR54) to initiate a PLC-IP3R-calcium cascade that modulates both potassium and NSC channels to initiate depolarization in GnRH neurons.

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Cited by

Metadata

Authors
Liu, X., Lee, K., & Herbison, A. E.
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2008-05-15
Volume
149
Issue
9
Pages
4605-4614
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2008-0321
OpenAlex
W1991847642
Cited by
270
References
5
FWCI
21.73
Type
journal article
Language
en
Open access
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