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

• Published in: Epilepsy research Vol. 70; no. 2; pp. 172 - 183
• Main Authors: Wang, Jijiang, Chen, Yonghua, Li, Keyong, Hou, Lili
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2006; Elsevier
• Subjects: Animals; Animals, Newborn; Anticonvulsants. Antiepileptics. Antiparkinson agents; Arrhythmias, Cardiac - physiopathology; Biological and medical sciences; Brain Stem - drug effects; Brain Stem - physiopathology; Cardiac; Cerebrospinal Fluid; Death, Sudden, Cardiac; Epilepsy; GABA; GABA Antagonists - pharmacology; Glycine; Glycine Agents - pharmacology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Neurons - drug effects; Neurons - physiology; Neuropharmacology; Nucleus ambiguus; Parasympathetic Nervous System - physiopathology; Patch-Clamp Techniques; Pharmacology. Drug treatments; Picrotoxin - pharmacology; Rats; Rats, Sprague-Dawley; Seizures - physiopathology; Strychnine - pharmacology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vagal activity; GABA; Nucleus ambiguus; Glycine; Epilepsy; Cardiac; Vagal activity; Fluorescent tracer; Breathing rate; Configuration; Rat; Arrhythmia; Central nervous system; Electrophysiology; Cardiovascular disease; Patch clamp method; Epileptic seizure; Gabaergic receptor; Intermittent; Heart disease; Voltage; Inward current; Human; Nervous system diseases; Cardiocirculatory arrest; Sudden death; Rodentia; Excitability disorder; Cerebral disorder; Vertebrata; Mammalia; Neuron; Newborn; Aminoacid; Animal; Central nervous system disease; Neurotransmitter; Asystole; Neurotransmission
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2006.04.003

In patients of epilepsy a proportion of unexplained sudden deaths had been attributed to neurogenic arrhythmias. Although some evidence has suggested that epileptogenic activation of the cardiac parasympathetic nerves, which is revealed by ictal bradyarrhythmias or cardiac asystole, might be very critical in causing sudden deaths of patients of epilepsy the firing behavior of cardiac parasympathetic neurons (CPNs) during epileptic attack is not known. In the present study fluorescent tracer was injected into the cardiac sac of newborn rats to retrogradely label the parasympathetic neurons in the nucleus ambiguus (NA). The fluorescence-labeled NA neurons were further examined using whole-cell patch-clamp method in medulla slices with respiratory-like rhythm, and those with an inspiratory-related increase of the mixed inhibitory synaptic activity were identified as CPNs. We have demonstrated that blockade of the GABAergic and the glycinergic receptors in medulla slices evoked intermittent seizure-like firing of CPNs under current-clamp configuration, and evoked intermittent excitatory inward currents (IEICs) under voltage-clamp configuration. These results have given new evidence that CPNs might fire in a seizure-like pattern during epileptic attack, which might be responsible for the neurogenic ictal bradyarrhythmias, cardiac asystole, or even the sudden deaths of patients of epilepsy.