5-HT1A/7 receptor agonist excites cardiac vagal neurons via inhibition of both GABAergic and glycinergic inputs.
OBJECTIVE
To study the synaptic mechanisms involved in the 5-hydroxytryptamine1A/7 (5-HT1A/7) receptor-mediated reflex control of cardiac vagal preganglionic neurons (CVPN).


METHODS
CVPN were retrogradely labeled and identified in brain stem slices of newborn rats, and their synaptic activity was examined using whole-cell patch-clamp.


RESULTS
8-Hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), an agonist of 5-HT1A/7 receptors, had no effect on the glutamatergic inputs of CVPN. In contrast, it significantly decreased the frequency and the amplitude of both the GABAergic and the glycinergic spontaneous inhibitory postsynaptic currents (sIPSC). 8-OH-DPAT also caused significant amplitude decrease of the GABAergic currents evoked by stimulation of the nucleus tractus solitarius. Both the frequency inhibition and the amplitude inhibition of the GABAergic and the glycinergic sIPSC by 8-OH-DPAT had dose-dependent tendencies and could be reversed by WAY-100635, an antagonist of 5-HT1A/7 receptors. In the pre-existence of tetrodotoxin, 8-OH-DPAT had no effect on the GABAergic or the glycinergic miniature inhibitory postsynaptic currents, and had no effect on the GABAergic or the glycinergic currents evoked by exogenous GABA or glycine.


CONCLUSIONS
The 5-HT1A/7 receptor agonist excites CVPN indirectly via the inhibition of both the GABAergic and glycinergic inputs. These findings have at least in part revealed the synaptic mechanisms involved in the 5-HT1A/7 receptor-mediated reflex control of cardiac vagal nerves in intact animals.
Chen
Yong-Hua
YH
The State Key Laboratory of Medical Neurobiology, Fudan University Shanghai Medical College, Shanghai 200032, China.
Hou
Li-Li
LL
Wang
Ji-Jiang
JJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005998:Glycine / Q000502:physiology; D006321:Heart / Q000294:innervation*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D005680:gamma-Aminobutyric Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005998:Glycine