Effects of extracellular ATP were investigated in cultured rat hippocampal neurons using whole-cell voltage-clamp techniques. When a depolarizing step to +10 mV was applied from a holding potential of -60 mV, an outward K+ current was activated. ATP (3 to 300 μM) reduced the K+ current. Among adenosine derivatives, ADP (100 μM) slightly inhibited the K+ current, and AMP or adenosine (100 μM) was ineffective. UTP was as potent as ATP and α,β-methylene ATP was less effective than ATP. The inhibition by ATP of the K+ current was abolished by inclusion of 2 mM GDPβS in the intracellular solution. The results indicate that ATP inhibits K+ channels in rat hippocampal neurons through UTP-responsive P2-purinoceptors coupled with GTP-binding proteins.
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