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

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Abstract
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. 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. 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. 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. 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.