strychnine and Hypercapnia

The respiratory role of GABA(A), GABA(B) and glycine receptors within the Bötzinger complex (BötC) and the pre-Bötzinger complex (preBötC) was investigated in alpha-chloralose-urethane anesthetized, vagotomized, paralysed and artificially ventilated rabbits by using bilateral microinjections (30-50 nl) of GABA and glycine receptor agonists and antagonists. GABA(A) receptor blockade by bicuculline (5mM) or gabazine (2mM) within the BötC induced strong depression of respiratory activity up to apnea. The latter was reversed by hypercapnia. Glycine receptor blockade by strychnine (5mM) within the BötC decreased the frequency and amplitude of phrenic bursts. Bicuculline microinjections into the preBötC caused decreases in respiratory frequency and the appearance of two alternating different levels of peak phrenic activity. Strychnine microinjections into the preBötC increased respiratory frequency and decreased peak phrenic amplitude. GABA(A), but not glycine receptor antagonism within the preBötC restored respiratory rhythmicity during apnea due to bicuculline or gabazine applied to the BötC. GABA(B) receptor blockade by CGP-35348 (50mM) within the BötC and the preBötC did not affect baseline respiratory activity, though microinjections of the GABA(B) receptor agonist baclofen (1mM) into the same regions altered respiratory activity. The results show that only GABA(A) and glycine receptors within the BötC and the preBötC mediate a potent control on both the intensity and frequency of inspiratory activity during eupneic breathing. This study is the first to provide evidence that these inhibitory receptors have a respiratory function within the BötC.

Topics: Animals; Bicuculline; GABA Antagonists; GABA-A Receptor Agonists; Glycine Agents; Hypercapnia; Male; Microinjections; Muscimol; Organophosphorus Compounds; Pyridazines; Rabbits; Receptors, GABA; Receptors, Glycine; Respiratory Center; Respiratory Physiological Phenomena; Strychnine; Time Factors

The 'switching model' for generation of respiratory rhythms holds that gasping represents the release of a rostral medullary pacemaker mechanism from the pontomedullary neuronal circuit that generates eupnea. In a perfused preparation of the decerebrate juvenile rat, exposure to ischemia or hypoxic-hypercapnia caused an alteration in integrated phrenic activity from the incrementing pattern of eupnea to the decrementing pattern of gasping. The time required to elicit gasping was not altered by multiple exposures to ischemia or hypoxic-hypercapnia. Furthermore, this time to gasping was not altered following addition to the perfusate of increasing concentrations of bicuculline or picrotoxin; both block GABA(A) receptors. Addition to the perfusate of strychnine, a glycine antagonist, significantly shortened the duration of ischemia or hypoxic-hypercapnia required to elicit gasping. These results support the concept that a loss of inhibitory glycinergic transmission is a critical factor in release of pacemaker mechanisms for gasping from the pontomedullary neuronal circuit for eupnea.

Topics: Animals; GABA-A Receptor Antagonists; Hypercapnia; Hypoxia; In Vitro Techniques; Ischemia; Rats; Receptors, GABA-A; Receptors, Glycine; Respiration; Strychnine

In decerebrate, paralyzed and vagotomized cats, we recorded activities of hypoglossal and phrenic nerves and of the mylohyoid branch of the trigeminal nerve. At normocapnia, a respiratory-modulated trigeminal discharge could be discerned in most cats. This discharge was characterized by a diminution of activity during neural inspiration and a peak in expiration. In hypercapnia or hypoxia, peak activity increased and its time of occurrence moved to late inspiration. Augmentations of peak trigeminal, hypoglossal and phrenic activities were proportional. Peak trigeminal and hypoglossal activities increased more than phrenic following administrations of protriptyline, strychnine and, in some cats, cyanide or doxapram. Peak trigeminal activity fell more than phrenic after diazepam. Pentobarbital or halothane reduced peak hypoglossal, but not trigeminal, activity more than phrenic. However, after these anesthetics, trigeminal activity became restricted to the inspiratory-expiratory junction. We conclude that trigeminal and hypoglossal activities are more dependent upon processes within the reticular formation than is the bulbospinal-phrenic system. Central and peripheral chemoreceptor influences are distributed equivalently upon trigeminal, hypoglossal and phrenic motoneurons.

Topics: Animals; Cats; Chemoreceptor Cells; Decerebrate State; Diazepam; Doxapram; Electromyography; Electrophysiology; Female; Halothane; Hypercapnia; Hypoglossal Nerve; Hypoxia; Male; Pentobarbital; Phrenic Nerve; Protriptyline; Respiration; Strychnine; Trigeminal Nerve

Injection of subconvulsive doses of strychnine blocking the inhibitory synapses significantly increases the reflex activity of the respiratory muscle evoked by stimulation of the sciatic nerve as well as by inhalation of hypercapnic gas mixture. Thus the inhibitory synapses prevent the extreme hypocapnia evoked by hyperventilation.

Topics: Animals; Cats; Hypercapnia; Hyperventilation; Neural Inhibition; Reflex; Respiration; Sciatic Nerve; Strychnine; Synapses

Injection of a subconvulsive dose of strychnine (which blocked the inhibitory synapses) increases respiratory muscle activity evoked by stimulation of a sciatic nerve as well as by inhalation of hypercapnic gas mixture. Thus the inhibitory synapses prevent an excessive hyperventilation.

Topics: Animals; Cats; Diaphragm; Hypercapnia; Hyperventilation; Neural Inhibition; Respiration; Strychnine

Topics: Animals; Autoradiography; Blood Pressure; Blood-Brain Barrier; Brain; Capillary Permeability; Carbon Dioxide; Cats; Hypercapnia; Methionine Sulfoximine; Oxygen; Partial Pressure; Pentylenetetrazole; Seizures; Serum Albumin, Radio-Iodinated; Strychnine; Sulfates; Sulfur Isotopes