Small molecule G-protein Arf1 in combination with phospholipase D (PLD) is essential for intracellular trafficking of the proteins from endoplasmic reticulum to Golgi apparatus. However, it is recently reported that it also regulate ionic channel activity presumably though recycling of the receptors and ionic channels at the cytoplasmic membrane. To examine possible involvement of Arf and subsequent PLD in regulation of receptor-induced responses in neuron, we recorded K⁺-current response induced by dopamine (DA) in the ganglion cells of Aplysia under conventional two-electrode voltage clamp. Intracellular application of brefeldin A, a specific blocker of Arf GEF, significantly depressed the K⁺-current response to DA. The DA-induced response was also inhibited by injection of 2-(4-fluorobenzoilamino)- benzoic methyl ester (Exo1), an activator of GAP for Arf1. Intracellular injection of N-terminal peptide of Arf1 markedly suppressed the DA-induced response. In contrast, application of those of Arf6 did not affect the response to DA. Furthermore, intracellular application of α-synuclein, a specific blocker of PLD, significantly depressed the K⁺-current response to DA. In contrast, all these reagents had no significant effect on the Na⁺-current response induced by acetylcholine in the same type of cells. These results suggest that Arf1 and subsequent PLD may regulate the K⁺-current response induced by DA. [J Physiol Sci. 2006;56 Suppl:S86]