Repetitive applications of ATP potentiate potassium current by Ca2+/calmodulin kinase in cultured rat hippocampal neurons.

ATP evoked whole-cell potassium currents in hippocampal neurons. The second application of ATP to the same cell potentiated the current amplitude to around 140% and the current potentiation was maintained by further applications. A calmodulin inhibitor, W-7, or a selective Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor, KN-62, inhibited the current potentiation, although a selective protein kinase C inhibitor, GF109203X, or a selective cAMP-dependent protein kinase inhibitor, H-89, had no effect. In addition, ATP enhanced intracellular free Ca2+ concentration, which may activate CaMKII, but this enhancement was blocked by repetitive applications. These results provide an indication that CaMKII may be involved in the current potentiation by repetitive applications of ATP.