Lack of an endogenous GABAA receptor-mediated tonic current in hypoglossal motoneurons. 2012

J M Numata, and J F M van Brederode, and A J Berger
University of Washington, School of Medicine, Department of Physiology & Biophysics, Box 357290, Seattle, WA 98195-7290, USA.

Tonic GABAA receptor-mediated current is an important modulator of neuronal excitability, but it is not known if it is present in mammalian motoneurons. To address this question studies were performed using whole-cell patch-clamp recordings from mouse hypoglossal motoneurons (HMs) in an in vitro slice preparation. In the presence of blockers of glutamatergic and glycinergic receptor-mediated transmission application of SR-95531 or bicuculline, while abolishing GABAA receptor-mediated phasic synaptic currents, did not reveal a tonic GABAA receptor-mediated current. Additionally, blockade of both GAT-1 and GAT-3 GABA transporters did not unmask this tonic current. In contrast, application of exogenous GABA (1 to 15 μm) resulted in a tonic GABAergic current that was observed when both GAT-1 and GAT-3 transporters were simultaneously blocked, and this current was greater than the sum of the current observed when each transporter was blocked individually. We also investigated which GABAA receptor subunits may be responsible for the current. Application of the δ subunit GABAA receptor agonist THIP resulted in a tonic GABAA receptor current. Application of the δ subunit modulator THDOC resulted in an enhanced tonic current. Application of the α5 subunit GABAA receptor inverse agonist L-655,708 did not modulate the current. In conclusion, these data show that HMs have tonic GABAA receptor-mediated current. The level of GABA in the vicinity of GABAA receptors responsible for this current is regulated by GABA transporters. In HMs a tonic current in response to exogenous GABA probably arises from activation of GABAA receptors containing δ subunits.

UI MeSH Term Description Entries
D009046 Motor Neurons Neurons which activate MUSCLE CELLS. Neurons, Motor,Alpha Motorneurons,Motoneurons,Motor Neurons, Alpha,Neurons, Alpha Motor,Alpha Motor Neuron,Alpha Motor Neurons,Alpha Motorneuron,Motoneuron,Motor Neuron,Motor Neuron, Alpha,Motorneuron, Alpha,Motorneurons, Alpha,Neuron, Alpha Motor,Neuron, Motor
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
D001933 Brain Stem The part of the brain that connects the CEREBRAL HEMISPHERES with the SPINAL CORD. It consists of the MESENCEPHALON; PONS; and MEDULLA OBLONGATA. Brainstem,Truncus Cerebri,Brain Stems,Brainstems,Cerebri, Truncus,Cerebrus, Truncus,Truncus Cerebrus
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
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
D050485 GABA Plasma Membrane Transport Proteins A family of plasma membrane neurotransmitter transporter proteins that regulates extracellular levels of the inhibitory neurotransmitter GAMMA-AMINOBUTYRIC ACID. They differ from GABA RECEPTORS, which signal cellular responses to GAMMA-AMINOBUTYRIC ACID. They control GABA reuptake into PRESYNAPTIC TERMINALS in the CENTRAL NERVOUS SYSTEM through high-affinity sodium-dependent transport. GABA Transporter,Neurotransmitter Transport Proteins, GABA-Specific,Neurotransmitter Transporters, GABA-Specific,GABA Plasma Membrane Transporter Proteins,GABA Transporter 1,GABA Transporter 2,GABA Transporter 3,GABA Transporter 4,GABA Transporters,GAT-1 Transporter,GAT-2 Transporter,GAT-3 Transporter,GAT-4 Transporter,GAT1 Transporter,GAT2 Transporter,GAT3 Transporter,Gamma-Aminobutyric Acid Plasma Membrane Transport Proteins,GABA-Specific Neurotransmitter Transporters,GAT 1 Transporter,GAT 2 Transporter,GAT 3 Transporter,GAT 4 Transporter,Gamma Aminobutyric Acid Plasma Membrane Transport Proteins,Neurotransmitter Transport Proteins, GABA Specific,Neurotransmitter Transporters, GABA Specific,Transporter 2, GABA,Transporter, GABA,Transporter, GAT-2,Transporter, GAT-4,Transporter, GAT2,Transporters, GABA,Transporters, GABA-Specific Neurotransmitter
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018682 GABA Agents Substances used for their pharmacological actions on GABAergic systems. GABAergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function. gamma-Aminobutyric Acid Agents,GABA Effect,GABA Effects,GABAergic Agent,GABAergic Agents,GABAergic Effect,GABAergic Effects,Acid Agents, gamma-Aminobutyric,Agent, GABAergic,Agents, GABA,Agents, GABAergic,Agents, gamma-Aminobutyric Acid,Effect, GABA,Effect, GABAergic,Effects, GABA,Effects, GABAergic,gamma Aminobutyric Acid Agents
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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