Actions of arginine polyamine on voltage and ligand-activated whole cell currents recorded from cultured neurones.

1 Toxins from invertebrates have proved useful tools for investigation of the properties of ion channels. In this study we describe the actions of arginine polyamine which is believed to be a close analogue of FTX, a polyamine isolated from the American funnel web spider, Agelenopsis aperta. 2 Voltage-activated Ca2+ currents and Ca2+-dependent Cl− currents recorded from rat cultured dorsal root ganglion neurones were reversibly inhibited by arginine polyamine (AP; 0.001 to 100 μm). Low voltage-activated T-type Ca2+ currents were significantly more sensitive to AP than high voltage-activated Ca2+ currents. The IC50 values for the actions of AP on low and high voltage-activated Ca2+ currents were 10 nm and 3 μm respectively. AP was equally effective in inhibiting high voltage-activated currents carried by Ba2+, Sr2+ or Ca2+. However, AP-induced inhibition of Ca2+ currents was attenuated by increasing the extracellular Ca2+ concentration from 2 mm to 10 mm. 3 The actions of AP on a Ca2+-independent K+ current were more complex, 1 μm AP enhanced this current but 10 μm AP had a dual action, initially enhancing but then inhibiting the K+ current. 4 γ-Aminobutyric acid-activated Cl− currents were also reversibly inhibited by 1 to 10 μm AP. In contrast N-methyl-d-aspartate currents recorded from rat cultured cerebellar neurones were greatly enhanced by 10 μm AP. 5 We conclude that at a concentration of 10 nm, AP is a selective inhibitor of low threshold T-type voltage-activated Ca2+ currents. However, at higher concentrations 1–10 μm AP interacts with ion channels or other membrane constituents to produce a variety of actions on both voltage and ligand gated ion channels.