GABA release by basket cells onto Purkinje cells, in rat cerebellar slices, is directly controlled by presynaptic purinergic receptors, modulating Ca2+ influx.
In many brain regions, Ca(2+) 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 (30microM) or suramin (12microM), 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 alpha,beta-methylene ATP. This suggests presynaptic facilitation of GABA release via P2XR-mediated Ca(2+) influx activated by endogenously released ATP. In contrast, activation of P2Y4 receptors (using UTP, 30microM, but not P2Y1 or P2Y6 receptor ligands) results in inhibition of GABA release. Immunological studies reveal the presence of most known P2Rs in >or=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 Ca(2+) permeability of the P2X receptor and the ability of ATP to influence intracellular Ca(2+) levels via P2Y receptor-mediated intracellular pathways make ATP the ideal transmitter for the multisite bidirectional modulation of the cerebellar cortical neuronal network.
Donato
Roberta
R
Department of Physiology, University College London, London, UK.
Rodrigues
Ricardo J
RJ
Takahashi
Michiko
M
Tsai
Ming Chi
MC
Soto
David
D
Miyagi
Kana
K
Villafuertes
Rosa Gomez
RG
Cunha
Rodrigo A
RA
Edwards
Frances A
FA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002525:Cerebellar Cortex / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011689:Purkinje Cells / Q000378:metabolism*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011963:Receptors, GABA-A; D017661:Receptors, Presynaptic; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D005680:gamma-Aminobutyric Acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate