Biomaterial Database

Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat. 1988

B W Connors, and R C Malenka, and L R Silva

Department of Neurology, Stanford University School of Medicine, CA 94305.

1. Pyramidal neurones from layers II and III of the rat primary somatosensory cortex and cat primary visual cortex were studied in vitro. Inhibitory postsynaptic potentials (IPSPs) and responses to exogenously applied gamma-aminobutyric acid (GABA) and its analogue baclofen were characterized. The results from rats and cats were very similar. 2. Single electrical stimuli to deep cortical layers evoked a sequence of PSPs in the resting neurone: (a) an initial, brief excitation (EPSP), (b) a short-latency, fast inhibition (the f-IPSP) and (c) a long-latency, more prolonged inhibition (the l-IPSP). The f-IPSP was accompanied by a large conductance increase (about 70-90 nS) and reversed polarity at -75 mV; the l-IPSP displayed a relatively small conductance increase (about 10-20 nS) and reversed at greater than -90 mV. 3. Focal application of GABA near the soma evoked a triphasic response when measured near the threshold voltage for action potentials: (a) the GABAhf (hyperpolarizing, fast) phase was very brief and was generated by a large conductance increase with a reversal potential of -78 mV, (b) the GABAd (depolarizing) phase also had a high conductance but reversed at -51 mV, (c) the GABAhl (hyperpolarizing, long-lasting) phase had a relatively low conductance and reversed at -70 mV. The GABAhf response was specifically localized to the soma, whereas the apical or basilar dendrites generated predominantly GABAd responses. 4. Baclofen, a selective GABAB receptor agonist, caused a small (about 2 mV), slow hyperpolarization of the resting potential, which reversed at -90 mV. Saturating baclofen doses increased membrane conductance by a maximum of about 12 nS. Baclofen depressed the amplitude and conductance of PSPs; when baclofen was focally applied near the soma. IPSPs were selectively depressed. 5. The GABAA receptor antagonists bicuculline methiodide or picrotoxin (10 microM) greatly depressed f-IPSPs, but either enhanced or did not affect l-IPSPs. Concomitantly, GABAhf and GABAd responses were antagonized, leaving a more prominent GABAhl response that reversed polarity at a more negative level of -87 mV. Baclofen responses were unaffected by bicuculline and picrotoxin. Extracellular barium abolished the baclofen response, and shifted the reversal potentials of the GABAd and GABAhl responses in the positive direction; the GABAhf response was unaffected. 6. Both focal GABA and f-IPSPs strongly depressed the intrinsic excitability of pyramidal neurones. Each greatly increased spike threshold and abolished or vastly reduced the capacity of the cells to fire repetitively during intense stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D009433	Neural Inhibition	The function of opposing or restraining the excitation of neurons or their target excitable cells.	Inhibition, Neural
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010852	Picrotoxin	A mixture of PICROTOXININ and PICROTIN that is a noncompetitive antagonist at GABA-A receptors acting as a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.	3,6-Methano-8H-1,5,7-trioxacyclopenta(ij)cycloprop(a)azulene-4,8(3H)-dione, hexahydro-2a-hydroxy-9-(1-hydroxy-1-methylethyl)-8b-methyl-, (1aR-(1aalpha,2abeta,3beta,6beta,6abeta,8aS,8bbeta,9S))-, compd. with (1aR-(1aalpha,2abeta,3beta,6beta,6abeta,8,Cocculin
D011963	Receptors, GABA-A	Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.	Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D002415	Cats	The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)	Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D005680	gamma-Aminobutyric Acid	The most common inhibitory neurotransmitter in the central nervous system.	4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001418	Baclofen	A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.	Baclophen,Chlorophenyl GABA,Apo-Baclofen,Atrofen,Ba-34,647,Ba-34647,Baclofen AWD,Baclofène-Irex,Baclospas,CIBA-34,647-BA,Clofen,Gen-Baclofen,Genpharm,Lebic,Lioresal,Liorésal,Nu-Baclo,PCP-GABA,PMS-Baclofen,beta-(Aminomethyl)-4-chlorobenzenepropanoic Acid,beta-(p-Chlorophenyl)-gamma-aminobutyric Acid,AWD, Baclofen,Apo Baclofen,ApoBaclofen,Ba34,647,Ba34647,Baclofène Irex,BaclofèneIrex,CIBA34,647BA,GABA, Chlorophenyl,Gen Baclofen,GenBaclofen,Nu Baclo,NuBaclo,PMS Baclofen,PMSBaclofen
D001464	Barium	An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.