ELECTROPHYSIOLOGICAL EFFECTS OF ATP ON BRAIN NEURONS

1 The electrophysiological effects of ATP on brain neurones are either due to the direct activation of P-2 purinoceptors by the unmetabolize d nucleotide or to the indirect activation of P-1 purinoceptors by the degradation product adenosine. 2 Two subtypes of P-2 purinoceptors ar e involved, a ligand-activated ion channel (P-2X) and a G protein-coup led receptor (P-2Y) Hence, the stimulation of P-2X purinoceptors leads to a cationic conductance increase, while the stimulation of P-2Y pur inoceptors leads to a G protein-mediated opening or closure of potassi um channels. 3 ATP may induce a calcium-dependent potassium current by increasing the intracellular Ca2+ concentration. This is due either t o the entry of Ca2+ via P-2X purinoceptors or to the activation of met abotropic P-2Y purinoceptors followed by signaling via the G protein/p hospholipase C/inositol 1,4,5-trisphosphate (IP3) cascade. Eventually, IP3 releases Ca2+ from its intracellular pools. 4 There is no convinc ing evidence for the presence of P-2U purinoceptors sensitive to both ATP and UTP, or pyrimidinoceptors sensitive to UTP only, in the centra l nervous system (CNS). 5 ATP-sensitive P-2X and P-2Y. purinoceptors s how a wide distribution in the CNS and appear to regulate important ne uronal functions.