title: Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.
abstract: Dexmedetomidine, an α2 adrenergic agonist, is a useful sedative but can also cause significant bradycardia. This decrease in heart rate may be due to decreased central sympathetic output as well as increased parasympathetic output from brainstem cardiac vagal neurons. In this study, using whole cell voltage clamp methodology, the actions of dexmedetomidine on excitatory glutamatergic and inhibitory GABAergic and glycinergic neurotransmission to parasympathetic cardiac vagal neurons in the rat nucleus ambiguus was determined. The results indicate that dexmedetomidine decreases both GABAergic and glycinergic inhibitory input to cardiac vagal neurons, with no significant effect on excitatory input. These results provide a mechanism for dexmedetomidine induced bradycardia and has implications for the management of this potentially harmful side effect.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The George Washington University, USA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Sharp
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, 2300 Eye St. NW, Washington, DC 20037, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, 2300 Eye St. NW, Washington, DC 20037, USA. Electronic address: dmendel@gwu.edu.
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000294:innervation*; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D020927:Dexmedetomidine; D005998:Glycine
keywords: Cardiac vagal neuron; Dexmedetomidine; Inhibitory; Neurotransmission