Pb2+ impairs GABAergic synaptic transmission in rat hippocampal slices: a possible involvement of presynaptic calcium channels.
Brain Res
; 1088(1): 93-100, 2006 May 09.
Article
en En
| MEDLINE
| ID: mdl-16630593
Pb2+ is a common pollutant that causes a wide variety of detrimental effects on developing central nervous system, including cognitive deficit. However, the mechanisms of Pb2+ neurotoxicity remain to be elucidated. GABAergic synaptic transmission in hippocampus is implicated in learning and memory. In the present study, we examined the effects of Pb2+ on GABA(A)-receptor-mediated inhibitory postsynaptic currents (IPSCs), recorded on CA1 pyramidal neurons in rat hippocampal slices, using whole-cell patch clamp recording. Pb2+ significantly inhibited the peak amplitude of evoked IPSCs and increased paired pulse ratio. In addition, Pb2+ (2-50 microM) significantly diminished the frequency of spontaneous IPSCs in a concentration-dependent manner with an IC(50) of 7.56 microM, without changing the amplitude of spontaneous IPSCs. However, Pb2+ (10 microM) did not alter the frequency and amplitude of miniature IPSCs. It was indicated that Pb2+ impaired GABAergic synaptic transmission via a presynaptic mechanism, inhibiting action potential-dependent GABA release. Interestingly, the inhibition of spontaneous IPSC frequency induced by 10 microM Pb2+ was significantly attenuated either in the presence of 100 muM Cd2+ or in a low-calcium (0.5 mM) bath. It suggested the involvement of voltage-gated calcium channels (VGCC) in Pb2+'s inhibition of GABA release. This study provided electrophysiological evidence from developing hippocampal slices to support that Pb2+ inhibited action potential-dependent GABA release by inhibiting presynaptic VGCC, which might be a mechanism for Pb2+ -induced cognitive deficit.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Canales de Calcio
/
Transmisión Sináptica
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Ácido gamma-Aminobutírico
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Hipocampo
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Plomo
Límite:
Animals
Idioma:
En
Revista:
Brain Res
Año:
2006
Tipo del documento:
Article
Pais de publicación:
Países Bajos