Regulation of the potassium current and cytosolic Ca2+ release induced by 2-methylthio ATP in hippocampal neurons.

A potent P2Y purinoceptor agonist, 2-methylthio ATP (2-MeSATP), produced whole-cell potassium currents through a purinoceptor linked to a pertussis toxin (PTX)-insensitive G-protein in rat hippocampal neurons. The currents were not affected by a selective protein kinase C or A inhibitor. Single channel recordings demonstrated that the potassium channel is activated without latency even in outside-out patches. These suggest that the channel may be regulated directly by the beta gamma subunits of a G-protein. In addition, 2-MeSATP enhanced intracellular free Ca2+ concentration ([Ca2+]i) with a very rapid initiation time. The [Ca2+]i increase was inhibited by a broad G-protein inhibitor, but not by a phospholipase C (PLC) inhibitor or an IP3 receptor antagonist. These indicate that this Ca2+ mobilization may be regulated by a mechanism independent of a PLC-mediated phosphatidylinositol signaling pathway.