β adrenergic receptor modulation of neurotransmission to cardiac vagal neurons in the nucleus ambiguus

Abstract

β adrenergic receptors are a class of G protein-coupled receptors that have essential roles in regulating heart rate, blood pressure, and other cardiorespiratory functions. Although the role of β adrenergic receptors in the peripheral nervous system is well characterized, very little is known about their role in the central nervous system despite being localized in many brain regions involved in autonomic activity and regulation. Since parasympathetic activity to the heart is dominated by cardiac vagal neurons (CVNs) originating in the Nucleus Ambiguus (NA), β adrenergic receptors localized in the NA represent a potential target for modulating cardiac vagal activity and heart rate. This study tests the hypothesis that activation of β adrenergic receptors alters the membrane properties and synaptic neurotransmission to CVNs. CVNs were identified in brainstem slices and membrane properties and synaptic events were recorded using the whole-cell-voltage-clamp technique. The non-selective β agonist isoproterenol significantly decreased inhibitory GABAergic and glycinergic, as well as excitatory glutamatergic neurotransmission to cardiac vagal neurons. In addition, the β1 selective receptor agonist dobutamine, but not β2 or β3 receptor agonists, significantly decreased inhibitory GABAergic and glycinergic and excitatory glutamatergic neurotransmission to CVNs. These decreases in neurotransmission to CVNs persisted in the presence of tetrodotoxin (TTX). These results provide a mechanism by which activation of adrenergic receptors in the brainstem can alter parasympathetic activity to the heart. Likely physiological roles for this adrenergic receptor activation are coordination of parasympathetic-sympathetic activity and β receptor mediated increases in heart rate upon arousal.

Resting high‐frequency heart rate variability is related to resting brain perfusion

“…Cerebral arteries are innervated by both sympathetic (superior cervical ganglion) and parasympathetic projections (otic and sphenopalatine ganglia; Goadsby & Edvinsson, 2002; Ter Laan, van Dijk, Elting, Staal, & Absalom, 2013), and cerebral arteries contain both adrenergic and cholinergic receptors, which modulate vascular tone and cerebral blood flow (Hamner, Tan, Lee, Cohen, & Taylor, 2010; Hamner, Tan, Tzeng, & Taylor, 2012; Ter Laan et al, 2013). Sympathetic modulation of vascular tone and cerebral blood flow may be inversely related to excitation of cardiac vagal neurons, and ultimately HF-HRV via sympathetic neuromodulating effects acting on the cholinergic vagal neurons in the nucleus ambiguous (Bateman, Boychuk, Philbin, & Mendelowitz, 2012; Boychuk, Bateman, Philbin, & Mendelowitz, 2011). Our finding that higher HF-HRV is related to greater whole brain perfusion may be indicative of diminished sympathetic adrenergic inhibition in the nucleus ambiguus and less sympathetic adrenergic vasoconstriction of cerebral arteries, resulting in higher resting cerebral perfusion.…”

Effects of VPAC1 activation in nucleus ambiguus neurons

“…The activity of nAmb neurons is modulated by G protein-coupled receptors agonists such as nociceptin (Venkatesan et al, 2002; Venkatesan et al, 2003), endomorphin 1 (Irnaten et al, 2003), enkephalin, dynorphin (Wang et al, 2004), orexin A (Dergacheva et al, 2005), isoproterenol and dobutamine (Bateman et al, 2012). We identified several peptides, including urocortin 3 (Brailoiu et al, 2012), nesfatin-1 (Brailoiu et al, 2013b), urotensin II (Brailoiu et al, 2014b), and irisin (Brailoiu et al, 2015), that activate neurons of Amb and produce bradycardia.…”

Adrenoreceptor modulation of oromotor pathways in the rat medulla

“…For example, ␤-adrenoreceptor activation can inhibit K ϩ channels, leading to postsynaptic depolarization Nicoll 1986a, 1986b), and thus could also lead to an increase in the frequency of EPSCs and IPSCs via presynaptic network activity (Bateman et al 2012).…”