Biomaterial Database

Blockade of gamma-aminobutyric acid-gated chloride current in frog sensory neurons by picrotoxin. 1988

M Inoue, and N Akaike

Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

The mechanism of picrotoxin (PTX) suppression of the gamma-aminobutyric acid (GABA)-gated Cl- current (ICl) was examined in frog sensory neurons using the 'concentration-clamp' technique. The activation phase of GABA-induced ICl showed little change with the concomitant application of 10(-5) M PTX; however, the inactivation phase was markedly facilitated. ICl produced by simultaneous application of GABA and PTX was non-competitively suppressed while the plateau current showed a mixed type of competitive and non-competitive inhibitions. When the neuron was pretreated with PTX, the peak current of ICl produced by the simultaneous application of PTX and GABA was gradually suppressed, but the suppression of plateau level of ICl was rapid and not affected by pretreatment time. Recovery was not influenced by the length of pretreatment but depended only slightly on wash time. A major part of recovery occurred through the reactivation of the inhibited GABA receptor-ionophore complex by GABA. The first application of 3 x 10(-6) M GABA, after the response to 3 x 10(-6) M GABA was suppressed by the concomitant application of PTX, produced ICl consisting of the rapid phase and the slowly developing phase. ICl produced by simultaneous application of 10(-5) M GABA and 10(-5) M PTX and by the first application of 10(-5) M GABA after the inhibition showed a similar voltage dependence to the control ICl. These results indicate that PTX has access to the binding site inside the Cl- channel either through open channels or with different efficacies through closed channels, and thereby inhibits the GABA response by modifying the gating process.

UI	MeSH Term	Description	Entries
D007473	Ion Channels	Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.	Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D008433	Mathematics	The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Mathematic
D009475	Neurons, Afferent	Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.	Afferent Neurons,Afferent Neuron,Neuron, Afferent
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
D002712	Chlorides	Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.	Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
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
D001001	Anura	An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae.	Bombina,Frogs and Toads,Salientia,Toad, Fire-Bellied,Toads and Frogs,Anuras,Fire-Bellied Toad,Fire-Bellied Toads,Salientias,Toad, Fire Bellied,Toads, Fire-Bellied
D018756	GABA Antagonists	Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.	gamma-Aminobutyric Acid Antagonists,GABA Antagonist,GABA Receptor Antagonists,Acid Antagonists, gamma-Aminobutyric,Antagonist, GABA,Antagonists, GABA,Antagonists, GABA Receptor,Antagonists, gamma-Aminobutyric Acid,Receptor Antagonists, GABA,gamma Aminobutyric Acid Antagonists