NO differentially regulates neurotransmission to premotor cardiac vagal neurons in the nucleus ambiguus.
NO is involved in the neural control of heart rate, and NO synthase expressing neurons and terminals have been localized in the nucleus ambiguus where parasympathetic cardiac vagal preganglionic neurons are located; however, little is known about the mechanisms by which NO alters the activity of premotor cardiac vagal neurons. This study examines whether the NO donor sodium nitroprusside ([SNP] 100 micromol/L) and precursor, l-arginine (10 mmol/L), modulate excitatory and inhibitory synaptic neurotransmission to cardiac vagal preganglionic neurons. Glutamatergic, GABAergic, and glycinergic activity to cardiac vagal neurons was examined using whole-cell patch-clamp recordings in an in vitro brain slice preparation in rats. Both SNP, as well as l-arginine, increased the frequency of GABAergic neurotransmission to cardiac vagal preganglionic neurons but decreased the amplitude of GABAergic inhibitory postsynaptic currents. In contrast, both l-arginine and SNP inhibited the frequency of glutamatergic and glycinergic synaptic events in cardiac vagal preganglionic neurons. SNP and l-arginine also decreased glycinergic inhibitory postsynaptic current amplitude, and this response persisted in the presence of tetrodotoxin. Inclusion of the NO synthase inhibitor 7-nitroindazole (100 mumol/L) prevented the l-arginine-evoked responses. These results demonstrate that NO differentially regulates excitatory and inhibitory neurotransmission, facilitating GABAergic and diminishing glutamatergic and glycinergic neurotransmission to cardiac vagal neurons.
Kamendi
Harriet
H
Department of Pharmacology and Physiology, George Washington University, 2300 Eye St, NW, Washington, DC 20037, USA.
Dergacheva
Olga
O
Wang
Xin
X
Huang
Zheng-Gui
ZG
Bouairi
Evguenia
E
Gorini
Christopher
C
Mendelowitz
David
D
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001339:Autonomic Fibers, Preganglionic; D002491:Central Nervous System Agents / Q000494:pharmacology*; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects; D018009:Receptors, Glycine / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
D002491:Central Nervous System Agents; D020030:Nitric Oxide Donors; D018079:Receptors, GABA; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; C069474:glutamine receptor; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine