[CITATION][C] GABA-depolarization of a sensory ganglion: antagonism by picrotoxin and bicuculline

WC De Groat - Brain Research, 1972 - Elsevier
Brain Research, 1972Elsevier
Presynaptic inhibition in the mammalian spinal cord is associated with a depolarization of
primary afferent terminals 6. Both the depolarization (PAD) and the inhibition are reduced by
the administration of picrotoxin 7 and bicuculline TM. Since these agents also block the
neuronal depressant actions of GABA1, s, 9 it has been suggested that GABA might be the
chemical mediator of the presynaptic inhibitory process 11. GABA administered
electrophoretically to central synapses, produces a hyperpolarization of neuronal …
Presynaptic inhibition in the mammalian spinal cord is associated with a depolarization of primary afferent terminals 6. Both the depolarization (PAD) and the inhibition are reduced by the administration of picrotoxin 7 and bicuculline TM. Since these agents also block the neuronal depressant actions of GABA1, s, 9 it has been suggested that GABA might be the chemical mediator of the presynaptic inhibitory process 11.
GABA administered electrophoretically to central synapses, produces a hyperpolarization of neuronal membranes2A, an action opposite of the one expected for a presynaptic inhibitory transmitter. However, its depressant actions on peripheral autonomic ganglia are accompanied by a negative ganglionic surface potential, a response indicative of an underlying depolarization of the ganglion cells 4, 5. This effect is also blocked by picrotoxin and bicuculline, but is unaffected by strychnine or cholinergic blocking agents4, 5. Thus, it seems that GABA has different actions on central and peripheral nerve cells; and interestingly, its peripheral actions resemble those occurring during presynaptic inhibition. In the present experiments, I have obtained evidence for a depolarizing action of GABA on neurons in the vagal sensory ganglion (nodose ganglion). This depolarization was also blocked by picrotoxin and bicuculline. The experiments were undertaken on the assumption that the soma of a sensory neurone might have similar amino acid receptors and might be affected by GABA in a similar manner as the central terminals of sensory neurons. If this assumption is correct then the present data would provide support for a presynaptic inhibitory action of GABA. The surgical and recording procedures used in these experiments have been described in detail in an earlier report 4. Cats were anesthetized with a mixture of sodium diallylbarbiturate (70 mg/kg), urethane (280 mg/kg) and monoethylurea (280 mg/kg) administered intraperitoneally. After intubation of the trachea, a deep cervical well was prepared by removal of portions of the trachea and esophagus. The left nodose ganglion was exposed and the vagus nerve peripheral and central to the ganglion was dissected free from underlying tissues and sectioned 14 cm from the ganglion. Potentials evoked by drugs were recorded from the surface of ganglia by means of bipolar silver-silver chloride electrodes. One electrode was placed in direct contact with the body of the ganglion, the other on the crushed end of the vagus nerve. Ganglionic potentials were amplified with a resistance-coupled amplifier, displayed on an oscilloscope and photographed on 35 mm film. In all records an upward deflection of the tracing indicates negativity of the ganglion (ganglionic depolarization). All major branches of the common carotid artery except those supplying the ganglion were ligated. Drugs were administered through a 27-gauge needle inserted into the common carotid artery. Animals were paralyzed with gallamine triethiodide and artificially respired. Rate and depth of respiration were adjusted to maintain end tidal CO2 at 3.5-49/00. The temperature of the animals was maintained at 36-38 C by external heating devices.
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