Format

Send to

Choose Destination
See comment in PubMed Commons below
Endocrinology. 2011 Apr;152(4):1551-61. doi: 10.1210/en.2010-1191. Epub 2011 Feb 1.

Tonic extrasynaptic GABA(A) receptor currents control gonadotropin-releasing hormone neuron excitability in the mouse.

Author information

1
Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, 561-756, Korea.

Abstract

It is well established that the GABA(A) receptor plays an important role in regulating the electrical excitability of GnRH neurons. Two different modes of GABA(A) receptor signaling exist: one mediated by synaptic receptors generating fast (phasic) postsynaptic currents and the other mediated by extrasynaptic receptors generating a persistent (tonic) current. Using GABA(A) receptor antagonists picrotoxin, bicuculline methiodide, and gabazine, which differentiate between phasic and tonic signaling, we found that ∼50% of GnRH neurons exhibit an approximately 15-pA tonic GABA(A) receptor current in the acute brain slice preparation. The blockade of either neuronal (NO711) or glial (SNAP-5114) GABA transporter activity within the brain slice revealed the presence of tonic GABA signaling in ∼90% of GnRH neurons. The GABA(A) receptor δ subunit is only found in extrasynaptic GABA(A) receptors. Using single-cell RT-PCR, GABA(A) receptor δ subunit mRNA was identified in GnRH neurons and the δ subunit-specific agonist 4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridin-3-ol was found to activate inward currents in GnRH neurons. Perforated-patch clamp studies showed that 4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridin-3-ol exerted the same depolarizing or hyperpolarizing effects as GABA on juvenile and adult GnRH neurons and that tonic GABA(A) receptor signaling regulates resting membrane potential. Together, these studies reveal the presence of a tonic GABA(A) receptor current in GnRH neurons that controls their excitability. The level of tonic current is dependent, in part, on neuronal and glial GABA transporter activity and mediated by extrasynaptic δ subunit-containing GABA(A) receptors.

PMID:
21285326
DOI:
10.1210/en.2010-1191
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Support Center