title: Contraction-sensitive skeletal muscle afferents inhibit arterial baroreceptor signalling in the nucleus of the solitary tract: role of intrinsic GABA interneurons.
abstract: Arterial baroreceptor and skeletal muscle receptor afferents relay sensory information to the nucleus of the solitary tract (NTS) during exercise. Previous studies have suggested that skeletal muscle afferent input inhibits baroreflex function; however, detailed information on the role of muscle afferents and GABAergic mechanisms in the NTS is limited. Furthermore, identification of specific afferent modalities that activate GABAergic neurons in the NTS remains unknown. In the present study, we examined the neuroanatomical and physiological interactions between spinal dorsal horn cells that transmit contraction-sensitive input from skeletal muscle and GABAergic interneurons in the NTS. Biotinylated dextran amine (BDA, 10%, 25-100 nL) microinjection into dorsal horn of the cervical spinal cord was combined with glutamate decarboxylase (GAD) immunohistochemistry to visualize the nature of the relationship of BDA-labeled fibers in the NTS with GAD immunoreactivity (GAD-ir). BDA-labeled axons and terminal processes were localized in the medial, commissural, dorsomedial and dorsolateral subdivisions of the caudal NTS. Moreover, BDA-labeled fibers were observed in close proximity to GAD-ir structures throughout these regions of the NTS. The physiological interaction between skeletal muscle receptor and arterial baroreceptor afferents was investigated using an arterially perfused, decerebrate rat preparation. Activation of skeletal muscle afferents by electrically evoked twitch contraction of the forelimb attenuated baroreflex responsiveness (BR, calculated as the ratio of changes in heart rate to systemic pressure) from -1.5+/-0.3 bpm.mm Hg(-1) to -0.1+/-0.1 bpm.mm Hg(-1) (control versus contraction, P<0.05, n=15). However, forelimb contraction failed to inhibit the reflex bradycardia evoked by activation of peripheral chemoreceptor afferents, indicating a reflex-specific action. Bilateral microinjection of bicuculline methiodide (BIC, 10 microM, 40-60 nL) into the caudal NTS restored baroreflex responsiveness during contraction (-1.6+/-0.2 versus -0.1+/-0.1 versus -1.5+/-0.2 bpm.mmHg(-1), control versus contraction versus contraction+BIC P<0.05, n=8). We conclude that activation of ascending spinal neurons from the cervical dorsal horn by contraction-sensitive skeletal muscle afferents selectively inhibits arterial baroreceptor signaling in the NTS via activation of a GABAergic mechanism.
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Gordon Scott Hall, Room 4116, Detroit, MI 48201, USA. jpotts@med.wayne.edu
authors.forename: J T
authors.initials: JT
authors.lastname: Potts
authors.forename: J F R
authors.initials: JF
authors.lastname: Paton
authors.forename: J H
authors.initials: JH
authors.lastname: Mitchell
authors.forename: M G
authors.initials: MG
authors.lastname: Garry
authors.forename: G
authors.initials: G
authors.lastname: Kline
authors.forename: P T
authors.initials: PT
authors.lastname: Anguelov
authors.forename: S M
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001158:Arteries / Q000502:physiology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D001710:Biotin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002452:Cell Count; D003911:Dextrans / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D010791:Phrenic Nerve / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D012966:Sodium Cyanide / Q000494:pharmacology; D017552:Solitary Nucleus / Q000166:cytology / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
chemical_list: D003911:Dextrans; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D007527:Isoenzymes; C076397:biotinylated dextran amine; D001710:Biotin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D012966:Sodium Cyanide; D001640:Bicuculline