Abstract
Aim:
To study the synaptic mechanisms involved in the 5-hydroxytryptamine 1A/7 (5-HT1A/7) receptor-mediated reflex control of cardiac vagal preganglionic neurons (CVPN).
Methods:
CVPN were retrogradely labeled and identified in brain stem slices of newborn rats, and their synaptic activity was examined using whole-cell patch-clamp.
Results:
8-Hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), an agonist of 5-HT1A/7 receptors, had no effect on the glutamatergic inputs of CVPN. In contrast, it significantly decreased the frequency and the amplitude of both the GABAergic and the glycinergic spontaneous inhibitory postsynaptic currents (sIPSC). 8-OH-DPAT also caused significant amplitude decrease of the GABAergic currents evoked by stimulation of the nucleus tractus solitarius. Both the frequency inhibition and the amplitude inhibition of the GABAergic and the glycinergic sIPSC by 8-OH-DPAT had dose-dependent tendencies and could be reversed by WAY-100635, an antagonist of 5-HT1A/7 receptors. In the pre-existence of tetrodotoxin, 8-OH-DPAT had no effect on the GABAergic or the glycinergic miniature inhibitory postsynaptic currents, and had no effect on the GABAergic or the glycinergic currents evoked by exogenous GABA or glycine.
Conclusion:
The 5-HT1A/7 receptor agonist excites CVPN indirectly via the inhibition of both the GABAergic and glycinergic inputs. These findings have at least in part revealed the synaptic mechanisms involved in the 5-HT1A/7 receptor-mediated reflex control of cardiac vagal nerves in intact animals.
Similar content being viewed by others
Article PDF
References
Loewy AD, Spyer KM . Central regulation of autonomic function. NY: Oxford University Press; 1990.
Mendelowitz D . Advances in parasympathetic control of heart rate and cardiac function. News Physiol Sci 1999; 14: 155–61.
Nosaka S, Yasunaga K, Tamai S . Vagal cardiac preganglionic neurons: distribution, cell types, and reflex discharges. Am J Physiol 1982; 243: R92–8.
Stuesse SL . Origins of cardiac vagal preganglionic fibers: a retrograde transport study. Brain Res 1982; 236: 15–25.
Standish A, Enquist LW, Escardo JA, Schwaber JS . Central neuronal circuit innervating the rat heart defined by transneuronal transport of pseudorabies virus. J Neurosci 1995; 15: 1998–2012.
Mendelowitz D . Firing properties of identified parasympathetic cardiac neurons in nucleus ambiguus. Am J Physiol 1996; 271: H2609–14.
Steinbusch HWM . Distribution of serotonin immunoreactivity in the central nervous system of the rat - cell bodies and terminals. Neuroscience 1981; 6: 557–618.
Sykes RM, Spyer KM, Izzo PN . Central distribution of substance P, calcitonin gene-related peptide, 5-hydroxytryptamine in vagal sensory afferents in the rat dorsal medulla. Neuroscience 1994; 59: 195–210.
Izzo PN, Jordan D, Ramage AG . Anatomical and pharmacological evidence supporting the involvement of serotonin in the central control of cardiac vagal motoneurones in the anaesthetized cat. J Physiol (London) 1988; 406: 19.
Izzo PN, Deuchars J, Spyer KM . Localization of cardiac vagal preganglionic motoneurones in the rat: Immunocytochemical evidence of synaptic inputs containing 5-hydroxytryptamine. J Comp Neurol 1993; 327: 572–83.
Dashwood MR, Gilbey MP, Jordan D, Ramage AG . Autoradiographic localization of 5-HT1A binding sites in the brainstem of the cat. Br J Pharmacol 1988; 94: 386.
Pazos A, Palacios JM . Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 1985; 346: 205–30.
Thor KB, Blitz-siebert A, Helke CJ . Autoradiographic localization of 5HT1 binding sites in autonomic areas of the rat dorsomedial medulla oblongata. Synapse 1992; 10: 217–27.
Pazos A, Probst A, Palacios JM . Serotonin receptors in the human brain. III. Autoradiographic mapping of serotonin-1 receptors. Neuroscience 1987; 21: 97–122.
Ramage AG, Fozard JR . Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT, ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats. Eur J Pharmacol 1987; 138: 179–91.
McCall RB, Escandon NA, Harris LT, Clement ME . Tolerance development to the vagal-mediated bradycardia produced by 5-HT1A receptor agonists. J Pharmacol Exp Ther 1994; 271: 777–81.
McCall RB, Escandon NA, Harris LT, Clement ME, Shepheard SL, Jordan D et al. Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat. Br J Pharmacol 1994; 111: 616–24.
Shepheard SL, Jordan D, Ramage AG . Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat. Br J Pharmacol 1994; 111: 616–24.
Sporton SCE, Shepheard SL, Jordan D, Ramage AG . Microinjections of 5-HT1A agonists into the dorsal motor vagal nucleus produce a bradycardia in the atenolol-pretreated anaesthetized rat. Br J Pharmacol 1991; 104: 467–70.
Chitravanshi VC, Calaresu FR . Additive effects of dopamine and 8-OH-DPAT microinjected into the nucleus ambiguus in eliciting vagal bradycardia in rats. J Auto Nerv Syst 1992; 41: 121–8.
Wang Y, Ramage AG . The role of central 5-HT (1A) receptors in the control of B-fibre cardiac and bronchoconstrictor vagal preganglionic neurones in anaesthetized cats. J Physiol (London) 2001; 536: 753–67.
Bogle RG, Pires JGP, Ramage AG . Evidence that central 5-HT1A receptors play a role in the von Bezold-Jarisch reflex in the rat. Br J Pharmacol 1990; 100: 757–60.
Skinner MR, Ramage AG, Jordan D . Effect of antagonism of central 5-HT1A receptors on baroreceptor and cardiopulmonary receptor reflexes in anaesthetized rabbits. J Physiol (London) 1998; 513P: 85.
Dando SB, Skinner MR, Jordan D, Ramage AG . Modulation of the vagal bradycardia evoked by stimulation of upper airway receptors by central 5-HT1 receptors in anaesthetized rabbits. Br J Pharmacol 1998; 125: 409–17.
Colino A, Halliwell JV . Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature 1987; 328: 73–7.
Melena J, Chidlow G, Osborne NN . Blockade of voltage-sensitive Na(+) channels by the 5-HT(1A) receptor agonist 8-OH-DPAT: possible significance for neuroprotection. Eur J Pharmacol 2000; 406: 319–24.
Wang J, Wang X, Irnaten M, Venkatesan P, Evans C, Baxi S, et al. Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons. J Neurophysiol 2003; 89: 2473–81.
Wang J, Irnaten M, Mendelowitz D . Characteristics of spontaneous and evoked GABAergic synaptic currents in cardiac vagal neurons in rats. Brain Res 2001; 889: 78–83.
Wang X, Dergacheva O, Kamendi H, Gorini C, Mendelowitz D . 5-Hydroxytryptamine 1A/7 and 4α receptors differentially prevent opioid-induced inhibition of brain stem cardiorespiratory function. Hypertension 2007; doi:10.1161/HYPERTENSIONAHA.107.091009.
Gatti PJ, Johnson TA, Phan P, Jordan IK, Coleman W, Massari VJ . The physiological and anatomical demonstration of functionally selective parasympathetic ganglia located in discrete fat pads on the feline myocardium. J Auton Nerv Syst 1995; 51: 255–99.
Grkovic I, Fernandez K, McAllen RM, Anderson CR . Misidentification of cardiac vagal pre-ganglionic neurons after injections of retrograde tracer into the pericardial space in the rat. Cell Tissue Res 2005; 321: 335–40.
Irnaten M, Neff RA, Wang J, Loewy AD, Mettenleiter TC, Mendelowitz D . Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP. J Neurophysiol 2001; 85: 435–8.
Neff RA, Wang J, Baxi S, Evans C, Mendelowitz D . Respiratory sinus arrhythmia: endogenous activation of nicotinic receptors mediates respiratory modulation of brainstem cardioinhibitory parasympathetic neurons. Circ Res 2003; 93: 565–72.
Bobker DH, Williams JT . Serotonin-mediated inhibitory postsynaptic potential in guinea-pig prepositus hypoglossi and feedback inhibition by serotonin. J Physiol 1990; 422: 447–62.
Wang J, Chen Y, Li K, Hou L . Blockade of inhibitory neurotransmission evoked seizure-like firing of cardiac parasympathetic neurons in brainstem slices of newborn rats: implications for sudden deaths in patients of epilepsy. Epilepsy Res 2006; 70: 172–83.
Browning KN, Travagli RA . Characterization of the in vitro effects of 5-hydroxytryptamine (5-HT) on identified neurons of the rat dorsal motor nucleus of the vagus (DMV). Br J Pharmacol 1999; 128: 1307–15.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the Shanghai Education and Development Foundation Shuguang Grant (No 03SG06) and the National Natural Science Foundation of China (No 30470690) to Ji-jiang Wang.
Rights and permissions
About this article
Cite this article
Chen, Yh., Hou, Ll. & Wang, Jj. 5-HT1A/7 receptor agonist excites cardiac vagal neurons via inhibition of both GABAergic and glycinergic inputs. Acta Pharmacol Sin 29, 529–538 (2008). https://doi.org/10.1111/j.1745-7254.2008.00745.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2008.00745.x