scholarly journals Conformational basis for the Li + ‐induced leak current in the rat γ‐aminobutyric acid (GABA) transporter‐1

2002 ◽  
Vol 544 (2) ◽  
pp. 447-458 ◽  
Author(s):  
Nanna MacAulay ◽  
Thomas Zeuthen ◽  
Ulrik Gether
Keyword(s):  
Aminobutyric Acid ◽  
Leak Current ◽  
Gaba Transporter ◽  
Gaba Transporter 1

scholarly journals A functional role for both γ‐aminobutyric acid (GABA) transporter‐1 and GABA transporter‐3 in the modulation of extracellular GABA and GABAergic tonic conductances in the rat hippocampus

2013 ◽  
Vol 591 (10) ◽  
pp. 2429-2441 ◽  
Author(s):  
Flavie Kersanté ◽  
Samuel C. S. Rowley ◽  
Ivan Pavlov ◽  
María Gutièrrez‐Mecinas ◽  
Alexey Semyanov ◽  
...  
Keyword(s):  
Functional Role ◽  
Rat Hippocampus ◽  
Aminobutyric Acid ◽  
Gaba Transporter ◽  
Gaba Transporter 1

scholarly journals Engineered Zn2+Switches in the γ-Aminobutyric Acid (GABA) Transporter-1

2001 ◽  
Vol 276 (44) ◽  
pp. 40476-40485 ◽  
Author(s):  
Nanna MacAulay ◽  
Annie Bendahan ◽  
Claus Juul Loland ◽  
Thomas Zeuthen ◽  
Baruch I. Kanner ◽  
...  
Keyword(s):  
Aminobutyric Acid ◽  
Gaba Transporter ◽  
Gaba Transporter 1

scholarly journals Elucidating Conformational Changes in the γ-Aminobutyric Acid Transporter-1

2009 ◽  
Vol 284 (24) ◽  
pp. 16226-16235 ◽  
Author(s):  
Anne-Kristine Meinild ◽  
Donald D. F. Loo ◽  
Soren Skovstrup ◽  
Ulrik Gether ◽  
Nanna MacAulay
Keyword(s):  
Conformational Changes ◽  
Aminobutyric Acid ◽  
Leak Current ◽  
Transient Currents ◽  
Transport Cycle ◽  
Sodium Dependent ◽  
Voltage Dependent ◽  
Intensity Changes ◽  
Gaba Transporter 1 ◽  
Insight Into

The GABA transporter-1 (GAT-1) has three current-generating modes: GABA-coupled current, Li+-induced leak current, and Na+-dependent transient currents. We earlier hypothesized that Li+ is able to substitute for the first Na+ in the transport cycle and thereby induce a distinct conformation in GAT-1 and that the onset of the Li+-induced leak current at membrane potentials more negative than −50 mV was due to a voltage-dependent conformational change of the Li+-bound transporter. In this study, we set out to verify this hypothesis and seek insight into the structural dynamics underlying the leak current, as well as the sodium-dependent transient currents, by applying voltage clamp fluorometry to tetramethylrhodamine 6-maleimide-labeled GAT-1 expressed in Xenopus laevis oocytes. MTSET accessibility studies demonstrated the presence of two distinct conformations of GAT-1 in the presence of Na+ or Li+. The voltage-dependent fluorescence intensity changes obtained in Li+ buffer correlated with the Li+-induced leak currents, i.e. both were highly voltage-dependent and only present at hyperpolarized potentials (<−50 mV). The transient currents correlated directly with the voltage-dependent fluorescence data obtained in sodium buffer and the associated conformational changes were distinct from those associated with the Li+-induced leak current. The inhibitor potency of SKF89976A of the Li+- versus Na+-bound transporter confirmed the cationic dependence of the conformational occupancy. Our observations suggest that the microdomain situated at the external end of transmembrane I is involved in different conformational changes taking place either during the binding and release of sodium or during the initiation of the Li+-induced leak current.

DISTRIBUTION OF GABA TRANSPORTER (GAT1) LEVELS IN THE BÖTZINGER COMPLEX AT THE EARLY STAGES OF POSTNATAL DEVELOPMENT IN RATS WITH PRENATAL SEROTONIN DEFICIENCY

2020 ◽  
pp. 7-12
Author(s):  
Л. И. Хожай
Keyword(s):  
Postnatal Development ◽  
Tryptophan Hydroxylase ◽  
Polyclonal Antibodies ◽  
Gaba Transporter ◽  
Early Stages ◽  
Bötzinger Complex ◽  
Neuronal Processes ◽  
Serotonin Deficiency ◽  
Gaba Transporter 1 ◽  
Primary Rabbit

Цель работы - исследование распределения уровня GAT-транспортера ГАМК в комплексе Бетцингера на разных сроках раннего постнатального развития крыс в норме и при пренатальном дефиците серотонина. Материал и методы. Работа проведена на лабораторных крысах линии Wistar. Снижение уровня эндогенного серотонина в эмбриональный период осуществляли методом ингибирования триптофан-гидроксилазы пара-хлорфенилаланином (пХФА). Выявление транспортного белка GAТпроводили посредством иммуногистохимической реакции с использованием первичных кроличьих поликлональных антител anti-GABA transporter1 (AbCam, Великобритания). Мозг исследовали на 5-, 10-е и 20-е сутки постнатального развития. Результаты. В комплексе Бетцингера на ранних сроках постнатального развития у контрольных животных отмечено колебание уровня GAT-транспортера ГАМК. На 1-й неделе жизни уровень GATбыл высоким как в сети отростков и терминалей, так и в синапсах. В течение 2-й недели жизни уровень GATснижался, а к концу 3-й недели - повышался вновь, достигая исходного уровня. Дефицит серотонина в пренатальный период вызывал у подопытных животных существенное увеличение уровня GATв нейропиле комплекса Бетцингера на всех изученных сроках постнатального развития. Выводы. Пренатальный дефицит серотонина приводит к существенному повышению уровня GAT-транспортера ГАМК в ранние сроки постнатального развития, что может приводить к изменению трансмиссии ГАМК и, как следствие, к нарушению баланса тормозных и возбуждающих эффектов в дыхательном ядре. Objective - to study the distribution of GABA transporter 1 (GAT) levels in the Bötzinger complex at the early stages of postnatal development in rats with prenatal serotonin deficiency. Materials and methods. The work was carried out on Wistar line laboratory rats. To reduce the level of endogenous serotonin in the embryonic period, the method of tryptophan hydroxylase inhibition by para-chlorophenylalanine (PCPA) (Sigma, USA) was used. The GAT1 transport protein was detected by immunohistochemical reaction with anti-GABA transporter1 primary rabbit polyclonal antibodies (AbCam, UK). The brain was examined on the 5, 10 and 20 day of postnatal development. Results. At the early stages of postnatal development, a fluctuation in the GAT1 level of the GABA transporter was noted in the Bötzinger complex of control animals. In the first postnatal week, the GAT level was high both in the network of neuronal processes and terminals, and in synapses. During the 2 week of life, the GAT1 level decreased, and by the end of the 3 week it increased again, reaching the initial level. Deficiency of serotonin in the prenatal period caused a significant increase in the level of GAT in the neuropil of the Bötzinger complex in experimental animals at all studied stages of postnatal development. Conclusions. Prenatal deficiency of serotonin leads to a significant increase in the GAT1 level at the early stages of postnatal development, which can lead to a change in the GABA transmission, and, as a result, to a disturbance in the balance of inhibitory and stimulatory effects in the respiratory nuclei.

GABA Transporter-1 (GAT1)-Deficient Mice: Differential Tonic Activation of GABAA Versus GABAB Receptors in the Hippocampus

2003 ◽  
Vol 90 (4) ◽  
pp. 2690-2701 ◽  
Author(s):  
Kimmo Jensen ◽  
Chi-Sung Chiu ◽  
Irina Sokolova ◽  
Henry A. Lester ◽  
Istvan Mody
Keyword(s):  
Gaba Release ◽  
Gabab Receptors ◽  
Acid Decarboxylase ◽  
Wild Type ◽  
Gaba Transporter ◽  
Inhibitory Neurotransmitter ◽  
Gaba Transporters ◽  
Gaba Transporter 1 ◽  
Glutamic Acid Decarboxylase 65 ◽  
Deficient Mice

After its release from interneurons in the CNS, the major inhibitory neurotransmitter GABA is taken up by GABA transporters (GATs). The predominant neuronal GABA transporter GAT1 is localized in GABAergic axons and nerve terminals, where it is thought to influence GABAergic synaptic transmission, but the details of this regulation are unclear. To address this issue, we have generated a strain of GAT1-deficient mice. We observed a large increase in a tonic postsynaptic hippocampal GABAA receptor-mediated conductance. There was little or no change in the waveform or amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) or miniature IPSCs. In contrast, the frequency of quantal GABA release was one-third of wild type (WT), although the densities of GABAA receptors, GABAB receptors, glutamic acid decarboxylase 65 kDa, and vesicular GAT were unaltered. The GAT1-deficient mice lacked a presynaptic GABAB receptor tone, present in WT mice, which reduces the frequency of spontaneous IPSCs. We conclude that GAT1 deficiency leads to enhanced extracellular GABA levels resulting in an overactivation of GABAA receptors responsible for a postsynaptic tonic conductance. Chronically elevated GABA levels also downregulate phasic GABA release and reduce presynaptic signaling via GABAB receptors thus causing an enhanced tonic and a diminished phasic inhibition.

scholarly journals Pharmacological Characterization of a Betaine/GABA Transporter 1 (BGT1) Inhibitor Displaying an Unusual Biphasic Inhibition Profile and Anti-seizure Effects

2020 ◽  
Vol 45 (7) ◽  
pp. 1551-1565
Author(s):  
Maria E. K. Lie ◽  
Stefanie Kickinger ◽  
Jonas Skovgaard-Petersen ◽  
Gerhard F. Ecker ◽  
Rasmus P. Clausen ◽  
...  
Keyword(s):  
Gaba Transporter ◽  
Pharmacological Characterization ◽  
Gaba Transporter 1

Significance of N-Glycosylation and Sialylation of GABA Transporter 1

2011 ◽  
Vol 30 (4-6) ◽  
pp. 206-217 ◽  
Author(s):  
J. Hu ◽  
W. Reutter ◽  
H. Fan
Keyword(s):  
Gaba Transporter ◽  
Gaba Transporter 1
Sign in / Sign up

Export Citation Format

Share Document