α1-adrenergic receptors facilitate inhibitory neurotransmission to cardiac vagal neurons in the nucleus ambiguus

Abstract

The cholinergic cardiac vagal neurons (CVNs), located in the nucleus ambiguus, are the origin of cardioinhibitory parasympathetic activity. Catecholaminergic neurons in nearby regions of the brainstem, including the C1 and C2 cell groups, are thought to play a key role in both arousing from sleep and maintaining wakefulness. Since norepinephrine (NE) could play an important role in influencing the activity of CVNs, particularly in response to sleeping/waking and arousal states, the present study investigated the contribution of α1-adrenergic receptor activation to augment inhibitory and/or blunt excitatory neurotransmission to CVNs. To test the effects of α1-adrenergic receptor activation, CVNs were labeled in rats by retrograde tracing and synaptic events were recorded by whole cell voltage clamp techniques in vitro. Prazosin, an inverse agonist of α1-adrenergic receptor, significantly decreased the frequency of both GABAergic and glycinergic neurotransmission to CVNs. Activation of α1-adrenergic receptors by the α1-adrenergic receptor agonists NE or phenylephrine (PE) both significantly increased GABAergic and glycinergic inhibitory event frequency. This effect was prevented by the sodium channel blocker tetrodotoxin (TTX). Activation of α1-adrenergic receptors did not alter glutamatergic neurotransmission to CVNs. This study indicates that α1-adrenergic receptor activation in the brainstem can facilitate inhibitory GABAergic and glycinergic neurotransmission to reduce CVN activity; this synaptic modulation may play a role in the tachycardia seen during NE-dependent behavioral arousal.

Threatening the heart and mind of gender stereotypes: Can imagined contact influence the physiology of stereotype threat?

“…Recent research shows activation of both alpha and beta-adrenergic receptors in the brain stem during states of stress and arousal also increases inhibition of cholinergic cardiac vagal neurons in the nucleus ambiguus via GABAergic and glycinergic neuromodulation (Bateman, Boychuk, Philbin, & Mendelowitz, in press;Boychuk, Bateman, Philbin, & Mendelowitz, 2011). Reduced cardiac vagal outflow functionally removes the parasympathetic brake from the heart and allows inherently faster cardiac pacemaker rhythms to increase heart rate (Porges, 2007).…”

GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus

“…For example, ACh-induced facilitation of GABAergic and/or glycinergic neurotransmission to CVNs in the nAmb may be involved in the generation of respiratory sinus arrhythmias (48). Activation of ␣ 1 -adrenergic receptors by norepinephrine facilitates GABAergic and glycinergic neurotransmission in the nAmb, reducing the activity of CVNs, which may explain tachycardia observed in norepinephrine- dependent behavioral arousal (4). One of the mechanisms by which CVNs are excited during hypoxia may be disinhibition of these neurons via withdrawal of GABAergic and glycinergic neurotransmission (15).…”

Pre- and postsynaptic modulations of hypoglossal motoneurons by α-adrenoceptor activation in wild-type andMecp2−/Ymice

“…The amplitude of sIPSCs was averaged, and frequency was calculated using minianalysis program. The concentration of 40 M was chosen as PE at 30 -50 M affects both GABA A and glycine receptors mediated-responses in cerebellar and nucleus ambiguous neurons (9,27). Bath application of PE increased the frequency (146 Ϯ 16.8% of control; P Ͻ 0.01, Student's t-test) but had no significant effect on amplitude (109 Ϯ 7.3% of control; P ϭ 0.12, Student's t-test) of sIPSCs in eight HNs (Fig.…”

“…In contrast to these postsynaptic effects, how presynaptic ␣ 1 -adrenoceptors act on synaptic transmission of HNs is poorly understood. Such presynaptic effects are likely to exist, as experimental evidence suggests that ␣ 1 -adrenoceptor agonists increase glycinergic transmission of motoneurons in the nucleus ambiguus and the spinal cord (3,9,20,24).The synaptic modulation of HNs may be affected in certain diseases. RTT is a neurodevelopmental disorder caused by disruptions of the MECP2 gene (21, 58).…”

“…In the brainstem and the spinal cord, activation of ␣ 1 -adrenoceptor produces a large variety of excitatory postsynaptic effects in motoneurons (52). In addition, there is also compelling evidence suggesting that the ␣ 1 -adrenoceptor mediates facilitation of GABAergic transmission of neurons in the hippocampus (40), frontal cortex (8), cerebellum (27), nucleus ambiguous (9), and olfactory bulb (43). In the hypoglossal nucleus, the ␣ 1 -adrenoceptor is involved in NE-mediated depolarization associated with an increase in input resistance, augmentation of spike frequency, and a decrease in afterhyperpolarization (6,46,49,60).…”