Endogenous angiotensin II facilitates GABAergic neurotransmission afferent to the Na+-responsive neurons of the rat median preoptic nucleus.
The median preoptic nucleus (MnPO) is densely innervated by efferent projections from the subfornical organ (SFO) and, therefore, is an important relay for the peripheral chemosensory and humoral information (osmolality and serum levels ANG II). In this context, controlling the excitability of MnPO neuronal populations is a major determinant of body fluid homeostasis and cardiovascular regulation. Using a brain slice preparation and patch-clamp recordings, our study sought to determine whether endogenous ANG II modulates the strength of the SFO-derived GABAergic inputs to the MnPO. Our results showed that the amplitude of the inhibitory postsynaptic currents (IPSCs) were progressively reduced by 44 +/- 2.3% by (Sar(1), Ile(8))-ANG II, a competitive ANG type 1 receptor (AT(1)R) antagonist. Similarly, losartan, a nonpeptidergic AT(1)R antagonist decreased the IPSC amplitude by 40.4 +/- 5.6%. The facilitating effect of endogenous ANG II on the GABAergic input to the MnPO was not attributed to a change in GABA release probability and was mimicked by exogenous ANG II, which potentiated the amplitude of the muscimol-activated GABA(A)/Cl(-) current by 53.1 +/- 11.4%. These results demonstrate a postsynaptic locus of action of ANG II. Further analysis reveals that ANG II did not affect the reversal potential of the synaptic inhibitory response, thus privileging a cross talk between postsynaptic AT(1) and GABA(A) receptors. Interestingly, facilitation of GABAergic neurotransmission by endogenous ANG II was specific to neurons responding to changes in the ambient Na(+) level. This finding, combined with the ANG II-mediated depolarization of non-Na(+)-responsive neurons reveals the dual actions of ANG II to modulate the excitability of MnPO neurons.
Henry
Mélaine
M
Centre de Recherche du Affilié au Centre Hospitalier Universitaire du Québec, Neurosciences and Faculté de Médecine, Université Laval, Québec, Canada.
Grob
Magali
M
Mouginot
Didier
D
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D002712:Chlorides; D018755:GABA Agonists; D044140:Receptor, Angiotensin, Type 1; D011963:Receptors, GABA-A; D000804:Angiotensin II; D005680:gamma-Aminobutyric Acid; D012964:Sodium