Activation of presynaptic GABAA receptors increases spontaneous glutamate release onto noradrenergic neurons of the rat locus coeruleus.
In order to further explore how GABA can modulate the excitability of noradrenergic neurons of the locus coeruleus (LC), we investigated the presence of GABA(A) receptors on glutamatergic nerve terminals and the functional consequences of their activation. We used mechanically dissociated immature rat LC neurons with adherent nerve terminals and patch-clamp recordings of spontaneous excitatory postsynaptic currents. Activation of presynaptic GABA(A) receptors by muscimol facilitated spontaneous glutamate release by activating tetrodotoxin-sensitive Na(+) channels and high-threshold Ca(2+) channels. Bumetanide (10 microM), a potent blocker of Na(+)-K(+)-Cl(-) cotransporter, diminished the muscimol-induced facilitatory action of glutamate release. Our results indicate that the Na(+)-K(+)-Cl(-) cotransporter accumulates Cl(-) inside the nerve terminals so that activation of presynaptic GABA(A) receptors causes depolarization. This GABA(A)-receptor-mediated modulation of spontaneous glutamatergic transmission is another mechanism by which GABA and its analogues can regulate the excitability and activity of noradrenergic neurons in the LC.
Koga
Hitoshi
H
Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ishibashi
Hitoshi
H
Shimada
Hideki
H
Jang
Il-Sung
IS
Nakamura
Tomoe Y
TY
Nabekura
Junichi
J
D000367:Age Factors; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009118:Muscimol / Q000494:pharmacology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D018755:GABA Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D018698:Glutamic Acid; D009638:Norepinephrine