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benzodiazepine receptors in cat primary somatosensory cortex
$7 IAP B L O C K S
PRESYNAPTIC
"GLUTAMATE-B"
RECEPTOR
A K I K O MIWA, N O B U F U M I KAWAI A N D M I C H I O UI*, Dept. of N e u r o b i o l . , Tokyo Metropolitan Inst. for Neuroscieces, 2-6 Musashidai, Fuchu-city, Tokyo, 183 a n d * D e p t . of Fhysiol. Chem., Fac. of Pharm. Sciences, Univ. of Tokyo, Tokyo 113, Japan In the lobster neuromuscular synapse, intra-axonal recording near the nerve terminal revealed that topically applied glutamate produced hyperpolarization in the presynaptic membrane. This presynaptic glutamate potential(PGP) reverses from hyperpolarization to depolarization at the membrane potential of around -100mY; and the reversal potential was more d e p e n d e n t on e x t e r n a l K than C1-. PGP was insensitive to a spider toxin (JSTX) which blocks postsynaptic glutamate potentials. Instead, PGP w a s e f f e c t i v e l y blocked by pertussis toxin (IAP). After exposure of the neuromuscular synapse to lAP( 1 - 1 0 ug/ml), PGP was gradually suppressed and finally abolished. The d e l a y and t i m e c o u r s e of t h e s u p p r e s s i o n of FGP w a s d e p e n d e n t on t h e d o s e o f IAP a p p l i e d . The resting conductance channels of the axonal membrane were unaffected b y IAP a n d t h e a c t i o n potential was a l m o s t the same before and after IAP a p p l i c a t i o n . In addition, IAP w a s w i t h o u t effect on t h e postsynaptic membrane, and the excitatory postsynaptic potentials as well as the glutamate-induced depolarizations were unaffected. Since a specific target of IAP-catalysed ADP-ribosylation is a guanine nucleotide regulatory protein (Ni) which is involved in receptor mediated inhibition of adenylate cyclase, blocking action o f lAP on PGP may r e s u l t from its ability to uncouple guanine nucleotide regulatory protei~ (Ni) from the glutamate receptor thereby abolishing the receptor-linked K channel activation. The p r e s e n t results suggest that a novel type of glutamate receptor, w h i c h s h o u l d be c a l l e d "Glutamate-_", is found in the presynaptic nerve+ terminal of lobster neuromuscular synapse and that the glutamate-induced K current is mediated by a GTP-binding protein.
A FUNCTIONAL ROLE OF GABA/BENZODIAZEPINE
RECEPTORS IN CAT PRIMARY SOMATOS~SORY CORTEX.
JUN-ICHIRO OKA and T. PHILIP HICKS *# . Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan, and =Department of Medical Physiology, Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada. Our recent experiments in cat somatosensory cortex have suggested the existence of intracortical inhibitory mechanisms mediated by 7-aminobutyric acid (GABA). The receptor for GABA is one component of the oligometric complex which includes the benzodiazepine (Bzd) binding site and the CI-ionophore. It was accordingly of interest to examine the effects of Bzds on the receptive field (RF)-size and response properties of cortical neurones with extracellular single unit recording combined with microiontophoretic drug administration, in order to search for a functional role of the presumptive receptor complex. Recordings have been made from 96 cells of 26 mongrel cats, anaesthetized with pentobarbiturate. Flurazepam elevated the threshold for somatic activation, depressed spontaneous activity and decreased RF-size. The latter effect was most often observed in large original RFs and at higher currents or with longer ejection times. Diazepam and midazolam exerted similar effects whereas ]ower doses of midazolam sometimes had the opposite effects. The Bzd antagonist, Ro 15-1788, decreased response threshold, increased spontaneous activity and sometimes enlarged RFs. This blocker reversed the inhibitory action of the Bzd agonists described above. The effects of GABA were potentiated with Bzds administered concurrently, and Ro 15-1788 showed a preventive action against this Bzd-enhanced component. In the experiments using airpuffstimulation for somatic activation, the inhibitory effects of Bzds and also the antagonistic effects of Ro 15-1788 were more frequently observed in tests with stimuli at a peripheral (boundary) zone of an RF than with those at a central zone. Spatial sun,nation of somatic sensory inputs on a cortex neuron was not likely to be selectively attenuated with Bzds, while the excitability of neurons was reduced. We conclude that the Bzd binding site is involved in cortical sensory processing and may functionally link with the GABAergic mechanisms, and that GABA/Bzd receptors may contribute to the modulation of somatosensory information through taking the RF-shaping action. Furthermore, it may be considered that such involvement of Bzd binding sites takes the form of mediating the sedative effects of Bzds. Oka, J.-I., Jang, E.K. and Hicks, T.P. (1986). Brain Res. 376: 194-198.
PRESYNAPTIC
"GLUTAMATE-B"
RECEPTOR
A K I K O MIWA, N O B U F U M I KAWAI A N D M I C H I O UI*, Dept. of N e u r o b i o l . , Tokyo Metropolitan Inst. for Neuroscieces, 2-6 Musashidai, Fuchu-city, Tokyo, 183 a n d * D e p t . of Fhysiol. Chem., Fac. of Pharm. Sciences, Univ. of Tokyo, Tokyo 113, Japan In the lobster neuromuscular synapse, intra-axonal recording near the nerve terminal revealed that topically applied glutamate produced hyperpolarization in the presynaptic membrane. This presynaptic glutamate potential(PGP) reverses from hyperpolarization to depolarization at the membrane potential of around -100mY; and the reversal potential was more d e p e n d e n t on e x t e r n a l K than C1-. PGP was insensitive to a spider toxin (JSTX) which blocks postsynaptic glutamate potentials. Instead, PGP w a s e f f e c t i v e l y blocked by pertussis toxin (IAP). After exposure of the neuromuscular synapse to lAP( 1 - 1 0 ug/ml), PGP was gradually suppressed and finally abolished. The d e l a y and t i m e c o u r s e of t h e s u p p r e s s i o n of FGP w a s d e p e n d e n t on t h e d o s e o f IAP a p p l i e d . The resting conductance channels of the axonal membrane were unaffected b y IAP a n d t h e a c t i o n potential was a l m o s t the same before and after IAP a p p l i c a t i o n . In addition, IAP w a s w i t h o u t effect on t h e postsynaptic membrane, and the excitatory postsynaptic potentials as well as the glutamate-induced depolarizations were unaffected. Since a specific target of IAP-catalysed ADP-ribosylation is a guanine nucleotide regulatory protein (Ni) which is involved in receptor mediated inhibition of adenylate cyclase, blocking action o f lAP on PGP may r e s u l t from its ability to uncouple guanine nucleotide regulatory protei~ (Ni) from the glutamate receptor thereby abolishing the receptor-linked K channel activation. The p r e s e n t results suggest that a novel type of glutamate receptor, w h i c h s h o u l d be c a l l e d "Glutamate-_", is found in the presynaptic nerve+ terminal of lobster neuromuscular synapse and that the glutamate-induced K current is mediated by a GTP-binding protein.
A FUNCTIONAL ROLE OF GABA/BENZODIAZEPINE
RECEPTORS IN CAT PRIMARY SOMATOS~SORY CORTEX.
JUN-ICHIRO OKA and T. PHILIP HICKS *# . Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan, and =Department of Medical Physiology, Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada. Our recent experiments in cat somatosensory cortex have suggested the existence of intracortical inhibitory mechanisms mediated by 7-aminobutyric acid (GABA). The receptor for GABA is one component of the oligometric complex which includes the benzodiazepine (Bzd) binding site and the CI-ionophore. It was accordingly of interest to examine the effects of Bzds on the receptive field (RF)-size and response properties of cortical neurones with extracellular single unit recording combined with microiontophoretic drug administration, in order to search for a functional role of the presumptive receptor complex. Recordings have been made from 96 cells of 26 mongrel cats, anaesthetized with pentobarbiturate. Flurazepam elevated the threshold for somatic activation, depressed spontaneous activity and decreased RF-size. The latter effect was most often observed in large original RFs and at higher currents or with longer ejection times. Diazepam and midazolam exerted similar effects whereas ]ower doses of midazolam sometimes had the opposite effects. The Bzd antagonist, Ro 15-1788, decreased response threshold, increased spontaneous activity and sometimes enlarged RFs. This blocker reversed the inhibitory action of the Bzd agonists described above. The effects of GABA were potentiated with Bzds administered concurrently, and Ro 15-1788 showed a preventive action against this Bzd-enhanced component. In the experiments using airpuffstimulation for somatic activation, the inhibitory effects of Bzds and also the antagonistic effects of Ro 15-1788 were more frequently observed in tests with stimuli at a peripheral (boundary) zone of an RF than with those at a central zone. Spatial sun,nation of somatic sensory inputs on a cortex neuron was not likely to be selectively attenuated with Bzds, while the excitability of neurons was reduced. We conclude that the Bzd binding site is involved in cortical sensory processing and may functionally link with the GABAergic mechanisms, and that GABA/Bzd receptors may contribute to the modulation of somatosensory information through taking the RF-shaping action. Furthermore, it may be considered that such involvement of Bzd binding sites takes the form of mediating the sedative effects of Bzds. Oka, J.-I., Jang, E.K. and Hicks, T.P. (1986). Brain Res. 376: 194-198.