Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat

Cara M Hildreth,Ann K Goodchild

doi:10.1186/1471-2202-11-128

Abstract

BackgroundCardiac vagal preganglionic neurons (CVPN) are responsible for the tonic, reflex and respiratory modulation of heart rate (HR). Although CVPN receive GABAergic and glutamatergic inputs, likely involved in respiratory and reflex modulation of HR respectively, little else is known regarding the functions controlled by ionotropic inputs. Activation of g-protein coupled receptors (GPCR) alters these inputs, but the functional consequence is largely unknown. The present study aimed to delineate how ionotropic GABAergic, glycinergic and glutamatergic inputs contribute to the tonic and reflex control of HR and in particular determine which receptor subtypes were involved. Furthermore, we wished to establish how activation of the 5-HT1A GPCR affects tonic and reflex control of HR and what ionotropic interactions this might involve.ResultsMicroinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN.ConclusionsWe conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN.

Highlights

Cardiac vagal preganglionic neurons (CVPN) are responsible for the tonic, reflex and respiratory modulation of heart rate (HR)
To verify that the sites targeted contained CVPN and that the entire rostro-caudal distribution of CVPN in the medulla could be targeted with two bilateral microinjections, bilateral microinjections of the GABAA agonist muscimol were made in 4 animals
A similar effect on the baroreflex has been described previously [35]. This confirms that the sites identified here are the source of cardiac vagal outflow and that the majority of CVPN could be targeted with two bilateral microinjections

Summary

Introduction

Cardiac vagal preganglionic neurons (CVPN) are responsible for the tonic, reflex and respiratory modulation of heart rate (HR). Activation of serotonin-1a/7, dopamine, μ-opioid or neurokinin-1 receptors within the NA decreases HR whereas activation of opioid-receptor like receptor-1 increases HR, demonstrating that activation of some GPCR can differentially alter the tonic level of HR [18,19,20,21]. The role of these GPCR, or for that matter others, in the reflex modulation of HR is not well understood. 5-HT1A receptor modulation of reflex cardiac vagal outflow is absent in the flinders sensitive line rat, an animal model of depression, which exhibits reduced BRS [23], highlighting the clinical importance of functional 5HT1A receptor control of cardiac vagal outflow

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