Endogenous GABA release inhibits the firing of adult gonadotropin-releasing hormone neurons.
The effect of endogenous gamma-aminobutyric acid (GABA)(A) receptor-mediated signaling on the excitability of adult male and female GnRH neurons was examined using gramicidin perforated-patch electrophysiology in GnRH-LacZ and GnRH-GFP (green fluorescent protein) transgenic mouse models. In both lines of mice, approximately 80% of GnRH neurons (n = 42) responded to the selective GABA(A) receptor antagonist bicuculline (20 microm) with a rapid and reversible membrane depolarization and/or increase in firing rate. Approximately 16% of GnRH neurons gave no response, and two neurons were inhibited by bicuculline. The same depolarizing responses (78%) were obtained from adult gonadectomized GnRH-GFP mice. The depolarizing response to bicuculline persisted in the presence of tetrodotoxin, demonstrating that even action potential-independent GABA release was acting to reduce GnRH neuron membrane potential. These observations show that endogenous GABA signaling through the GABA(A) receptor exerts a powerful net inhibitory effect upon the excitability of mature GnRH neurons.
Han
Seong-Kyu
SK
Laboratory of Neuroendocrinology, Babraham Institute, Cambridge CB2 4AT, U.K.
Todman
Martin G
MG
Herbison
Allan E
AE
D000200:Action Potentials; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D058787:GABA-A Receptor Antagonists; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016296:Mutagenesis; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009919:Orchiectomy; D010052:Ovariectomy; D011963:Receptors, GABA-A / Q000502:physiology; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D058787:GABA-A Receptor Antagonists; D008164:Luminescent Proteins; D011963:Receptors, GABA-A; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone; D005680:gamma-Aminobutyric Acid; D001616:beta-Galactosidase; D001640:Bicuculline