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GABA release by basket cells onto Purkinje cells, in rat cerebellar slices, is directly controlled by presynaptic purinergic receptors, modulating Ca2+ influx

2008; Elsevier BV; Volume: 44; Issue: 6 Linguagem: Inglês

10.1016/j.ceca.2008.03.006

1532-1991

R. J. Donato, Ricardo J. Rodrigues, Michiko Takahashi, Ming‐Chi Tsai, David Soto, Kana Miyagi, Rosa Gómez‐Villafuertes, Rodrigo A. Cunha, Frances A. Edwards,

Neuroscience and Neuropharmacology Research

In many brain regions, Ca2+ influx through presynaptic P2X receptors influences GABA release from interneurones. In patch-clamp recordings of Purkinje cells (PCs) in rat cerebellar slices, broad spectrum P2 receptor antagonists, PPADS (30 μM) or suramin (12 μM), result in a decreased amplitude and increased failure rate of minimal evoked GABAergic synaptic currents from basket cells. The effect is mimicked by desensitizing P2X1/3-containing receptors with α,β-methylene ATP. This suggests presynaptic facilitation of GABA release via P2XR-mediated Ca2+ influx activated by endogenously released ATP. In contrast, activation of P2Y4 receptors (using UTP, 30 μM, but not P2Y1 or P2Y6 receptor ligands) results in inhibition of GABA release. Immunological studies reveal the presence of most known P2Rs in ≥20% of GABAergic terminals in the cerebellum. P2X3 receptors and P2Y4 receptors occur in approximately 60% and 50% of GABAergic synaptosomes respectively and are localized presynaptically. Previous studies report that PC output is also influenced by postsynaptic purinergic receptors located on both PCs and interneurones. The high Ca2+ permeability of the P2X receptor and the ability of ATP to influence intracellular Ca2+ levels via P2Y receptor-mediated intracellular pathways make ATP the ideal transmitter for the multisite bidirectional modulation of the cerebellar cortical neuronal network.