Small G-protein Arf1 regulates K⁺-current responses induced by dopamine and FMRFamide in the ganglion cells of Aplysia

Abstract

Small molecule G-protein Arf family has a major role in regulation of intracellular trafficking of the proteins from Golgi apparatus to endoplasmic reticulum. However, it has recently been reported that it also regulates the activity of ionic channels in epithelial cells. To clarify possible involvement of Arf in G-protein coupled receptor (GPCR)-induced current responses, we examined the effects of several reagents specific to Arf1 or Arf6 on the K⁺- current responses induced by dopamine (DA) and Phe-Met-Arg-Phe-NH₂ (FMRFamide) in the ganglion cells of Aplysia by using conventional two-electrode voltage clamp method. Intracellular injection of Brefeldin A, a specific blocker of class I Arf, significantly depressed the K⁺-current responses to both DA and FMRFamide without affecting the Na⁺-current responses to acetylcholine in the same cell. The K⁺-current responses to DA and FMRFamide were also depressed by intracellular injection of 2-(4-fluorobenzoilamino)-benzoic methyl ester (Exo1), which is known to facilitate the GTPase activity for Arf1. Intracellular application of N-terminal peptide of Arf1, a competitive inhibitor of Arf1, markedly depressed the both K⁺-current responses. In contrast, injection of similar N-terminal peptide of Arf6 had no significant effect on the responses. These results suggest that Arf1 may commonly facilitate the production of the K⁺-current responses to both DA and FMRFamide. [Jpn J Physiol 55 Suppl:S146 (2005)]