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|Title:||Aluminium-induced impairment of Ca2+ modulatory action on GABA transport in brain cortex nerve terminals||Authors:||Cordeiro, J. M.
Silva, V. S.
Oliveira, C. R.
Gonçalves, P. P.
|Keywords:||Aluminium; Calcineurin; Ca2+/CaM signalling; Brain cortex||Issue Date:||2003||Citation:||Journal of Inorganic Biochemistry. 97:1 (2003) 132-142||Abstract:||The [gamma]-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 Ca2+/calmodulin-dependent protein phosphatase 2B (calcineurin). Aluminium is known to interfere with the Ca2+/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 Ca2+ downregulation of GABA transporter, when mediating uptake or release. Accordingly, aluminium inhibited Ca2+/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 Ca2+) or phosphorylation (absence of Ca2+ and/or presence of W-7, a selective calmodulin antagonist). In conclusion, aluminium-induced relief of Ca2+ modulatory action on GABA transporter may contribute significantly to modify GABAergic signalling during neurotoxic events in response to aluminium exposure.||URI:||http://hdl.handle.net/10316/3873||DOI:||10.1016/S0162-0134(03)00256-3||Rights:||openAccess|
|Appears in Collections:||FCTUC Ciências da Vida - Artigos em Revistas Internacionais|
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