Norepinphrine Increases Gabaergic Neurotransmission To Cardiac Vagal Neurons Via Activation Of Alpha 1 Adrenergic Receptors

Sudden Infant Death Syndrome likely results from sleep related cardiorespiratory abnormalities, particularly a dysregulation of parasympathetic heart rate control. However, little is known about the interactions between sleep/wake systems and cardioinhibitory vagal neurons (CVNs) located in the nucleus ambiguus that control cardiac parasympathetic output. Previous work has demonstrated that α2-adrenergic agonists significantly decreased GABAergic IPSC frequency in CVNs, but this does not explain norepinphrine's (NE) role in arousal related tachycardia. Therefore, the present study hypothesized that α1-adrenergic receptor activation would increase the frequency of GABAergic IPSCs to CVNs. In rat pups, CVNs were labeled by retrograde tracing and synaptic events were recorded by whole cell voltage clamp techniques in vitro. For all experiments, α2-adrenergic activity was prevented by the antagonist, atipamezole (1μM). Bath application of NE (20μM), NE with propranolol (a general β receptor antagonist, 10μM) or the specific α1-adrenergic receptor agonist, phenylephrine (50μM), all significantly increased the frequency of GABAergic inhibitory neurotransmission. Since augmented GABAergic neurotransmission to CVNs inhibits parasympathetic activity and increases heart rate, these data demonstrate a brainstem mechanism where NE release would increase heart rate during arousal from sleep. Supported by NIH grant: HL49965, 59895, 72006 to DM