title: Synaptic activation of cardiac vagal neurons by capsaicin sensitive and insensitive sensory neurons.
abstract: Little is known about the central circuitry involved in the sensory activation of cardioinhibitory vagal neurons (CVNs). To study the polysynaptic activation of CVNs from sensory neurons the postsynaptic currents in CVNs in the dorsal motor nucleus of the vagus (DMNX) were evoked by stimulation of the vagus nerve. In addition, the role of afferent A-fiber and C-fiber activation of CVNs was examined. CVNs were identified by a retrograde fluorescent tracer and were studied in an in vitro slice preparation using patch-clamp electrophysiology. Stimulation of the vagus nerve evoked excitatory postsynaptic currents in CVNs that were reversibly blocked by the NMDA antagonist D-2-amino-5-phosphonovalerate (AP5) and the non-NMDA antagonist 6-cyano-7-nitroquionoxaline-2,3-dione (CNQX). Vagal stimulation also evoked inhibitory postsynaptic currents (IPSCs) that were reversibly blocked by the GABA(A) antagonist gabazine. Capsaicin, which inactivates C-fibers, was used to examine the role of afferent A-fibers and C-fibers in the synaptic activation of CVNs. Capsaicin significantly (P<0.05) reduced the amplitude of evoked glutamatergic and GABAergic postsynaptic currents by 59% and 76%, respectively. The latency of the GABAergic response increased significantly (P<0.05) in the presence of capsaicin from 36+/-1 to 41+/-1 ms while the latency of the glutamatergic response (44+/-3 ms) was unaffected. There are three conclusions from this study. Stimulation of vagal afferents evokes both GABAergic and glutamatergic responses in CVNs, C-type afferent fibers are critical to the afferent stimulation of CVNs, and the A-fiber GABAergic pathway to CVNs may be more complex than the C-fiber GABAergic pathway.
authors.affiliation: Department of Pharmacology, George Washington University, 2300 Eye Street NW, 20037, Washington, DC, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Evans
authors.forename: Sunit
authors.initials: S
authors.lastname: Baxi
authors.forename: Robert
authors.initials: R
authors.lastname: Neff
authors.forename: Priya
authors.initials: P
authors.lastname: Venkatesan
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000502:physiology; D002211:Capsaicin / Q000378:metabolism; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D005973:Glutamine / Q000378:metabolism; D006321:Heart / Q000294:innervation*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D002211:Capsaicin