Aluminium-induced impairment of Ca 2+ modulatory action on GABA transport in brain cortex nerve terminals
The γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in vertebrate CNS. At GABAergic synapses, a high-affinity transporter exists, which is responsible for GABA reuptake and release during neurotransmission. GABA transporter activity depends on the phosphorylation/dephosphorylatio...
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Published in | Journal of inorganic biochemistry Vol. 97; no. 1; pp. 132 - 142 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
2003
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Subjects | |
Online Access | Get full text |
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Summary: | The γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in vertebrate CNS. At GABAergic synapses, a high-affinity transporter exists, which is responsible for GABA reuptake and release during neurotransmission. GABA transporter activity depends on the phosphorylation/dephosphorylation state, being modulated by Ca
2+/calmodulin-dependent protein phosphatase 2B (calcineurin). Aluminium is known to interfere with the Ca
2+/calmodulin signalling pathway. In this work, we investigate the action of aluminium on GABA translocation mediated by the high-affinity transporter, using synaptic plasma membrane (SPM) vesicles and synaptosomes isolated from brain cortex. Aluminium completely relieved Ca
2+ downregulation of GABA transporter, when mediating uptake or release. Accordingly, aluminium inhibited Ca
2+/calmodulin-dependent calcineurin activity present in SPM, in a concentration-dependent manner. The deleterious action of aluminium on the modulation of GABA transport was ascertained by comparative analysis of the aluminium effect on GABA uptake and release, under conditions favouring SPM dephosphorylation (presence of intracellular micromolar Ca
2+) or phosphorylation (absence of Ca
2+ and/or presence of W-7, a selective calmodulin antagonist). In conclusion, aluminium-induced relief of Ca
2+ modulatory action on GABA transporter may contribute significantly to modify GABAergic signalling during neurotoxic events in response to aluminium exposure. |
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ISSN: | 0162-0134 1873-3344 |
DOI: | 10.1016/S0162-0134(03)00256-3 |