ACTIVATION OF D2-LIKE DOPAMINE RECEPTORS INHIBITS GABA AND GLYCINERGIC NEUROTRANSMISSION TO PRE-MOTOR CARDIAC VAGAL NEURONS IN THE NUCLEUS AMBIGUUS

The parasympathetic control of heart rate arises from premotor cardiac vagal neurons (CVNs) located in the nucleus ambiguus (NA). Previous microinjection studies in NA show that dopamine evokes a decrease in heart rate, but the underlying mechanisms responsible for these responses were not identified. This study tested whether dopamine modulates inhibitory GABAergic and glycinergic and/or excitatory glutamatergic neurotransmission to CVNs. Retrogradely labeled CVNs were identified in an in vitro rat brainstem slice preparation and synaptic events were recorded using whole cell voltage clamp techniques. Bath application of dopamine (100 mu M) had no effect on excitatory synaptic events, but reversibly inhibited the frequency (but not amplitude) of GABAergic inhibitory postsynaptic currents (IPSCs) in CVNs. Similarly, dopamine (10 mu M and 100 mu M) inhibited glycinergic IPSC frequency by similar to 50% and 70% respectively. The reduction in inhibitory neurotransmission to CVNs by dopamine was prevented by the sodium channel blocker TTX (1 mu M) indicating that the dopamine mediated effects were action potential dependent. Dopamine evoked responses were mimicked by the D-2-like receptor agonist, Quinpirole but not D-1-like receptor agonist, SKF 38393. In addition, the dopamine mediated depression of inhibitory synaptic responses were prevented by the D-2-like receptor antagonist sulpiride, but not by D-1-like or adrenergic or serotonergic receptor antagonists, suggesting that these responses were D-2-like receptor mediated and not D-1-like or adrenergic or 5-HT receptor mediated. These data suggest that dopamine acts via dis-inhibition, and diminishes inhibitory GABAergic and glycinergic neurotransmission to CVNs, which would be predicted to increase parasympathetic activity to the heart and evoke a bradycardia. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.