The re-uptake of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA) in the central nervous system (CNS) is the primary function of the sodium- and chloride dependent GABA transporters. Among all four GABA transporters (GAT1-3 and BGT1), GAT1 is extensively investigated, as it is considered the primary regulator of GABA in the CNS. After GAT1, BGT1 (betaine/GABA transporter) has the most affinity for GABA, but still its physiological role in the brain is unclear and debatable. The nervous tissues can not only accumulate high concentrations of betaine (N-trimethylglycine), but also selectively prefer it over other osmolytes e.g., myo-inositol, creatine. Some recent studies in C. elegans show betaine regulated ion channels in the nervous system. Betaine is also being considered as treatment for schizophrenia. Our electrophysiological experiments on X. laevis oocytes expressing rGAT1, show the presence of inward transport currents in the presence of betaine. Despite acting like a substrate, when betaine is present, the changes in membrane voltages still elicited pre-steady state currents indicating a different transporter interaction mechanism than that of GABA. In competitive assay GABA and Betaine showed neither competition nor cooperation between them. Our preliminary results indicate betaine induced transport-like currents in GAT1. An actual influx of betaine needs to be confirmed, to understand the different behavior of GAT1 in the presence of the two substrates.

Is Betaine a substrate also for GABA transporter 1 (GAT1)?

Manan Bhatt
Primo
;
A. Di Iacovo
Membro del Collaboration Group
;
T. Romanazzi
Membro del Collaboration Group
;
R. Cinquetti
Methodology
;
C. Roseti
Supervision
;
E. Bossi
Supervision
2021-01-01

Abstract

The re-uptake of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA) in the central nervous system (CNS) is the primary function of the sodium- and chloride dependent GABA transporters. Among all four GABA transporters (GAT1-3 and BGT1), GAT1 is extensively investigated, as it is considered the primary regulator of GABA in the CNS. After GAT1, BGT1 (betaine/GABA transporter) has the most affinity for GABA, but still its physiological role in the brain is unclear and debatable. The nervous tissues can not only accumulate high concentrations of betaine (N-trimethylglycine), but also selectively prefer it over other osmolytes e.g., myo-inositol, creatine. Some recent studies in C. elegans show betaine regulated ion channels in the nervous system. Betaine is also being considered as treatment for schizophrenia. Our electrophysiological experiments on X. laevis oocytes expressing rGAT1, show the presence of inward transport currents in the presence of betaine. Despite acting like a substrate, when betaine is present, the changes in membrane voltages still elicited pre-steady state currents indicating a different transporter interaction mechanism than that of GABA. In competitive assay GABA and Betaine showed neither competition nor cooperation between them. Our preliminary results indicate betaine induced transport-like currents in GAT1. An actual influx of betaine needs to be confirmed, to understand the different behavior of GAT1 in the presence of the two substrates.
Bhatt, MANAN JUGGNU; Di Iacovo, A.; Romanazzi, T.; Cinquetti, R.; Roseti, C.; Bossi, E.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2130810
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