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Actions of arginine polyamine on voltage and ligand‐activated whole cell currents recorded from cultured neurones
Author(s) -
Scott Roderick H.,
Sweeney Marva I.,
Kobrinsky Evgeny M.,
Pearson Hugh A.,
Timms Graham H.,
Pullar Ian A.,
Wedley Susan,
Dolphin Annette C.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14315.x
Subject(s) - polyamine , biophysics , arginine , extracellular , chemistry , dorsal root ganglion , patch clamp , biochemistry , biology , anatomy , amino acid , receptor , dorsum
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 Ca 2+ currents and Ca 2+ ‐dependent Cl − currents recorded from rat cultured dorsal root ganglion neurones were reversibly inhibited by arginine polyamine (AP; 0.001 to 100 μ m ). Low voltage‐activated T‐type Ca 2+ currents were significantly more sensitive to AP than high voltage‐activated Ca 2+ currents. The IC 50 values for the actions of AP on low and high voltage‐activated Ca 2+ currents were 10 n m and 3 μ m respectively. AP was equally effective in inhibiting high voltage‐activated currents carried by Ba 2+ , Sr 2+ or Ca 2+ . However, AP‐induced inhibition of Ca 2+ currents was attenuated by increasing the extracellular Ca 2+ concentration from 2 m m to 10 m m . 3 The actions of AP on a Ca 2+ ‐independent K + current were more complex, 1 μ m AP enhanced this current but 10 μ m 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 μ m AP. In contrast N‐methyl‐ d ‐aspartate currents recorded from rat cultured cerebellar neurones were greatly enhanced by 10 μ m AP. 5 We conclude that at a concentration of 10 n m , AP is a selective inhibitor of low threshold T‐type voltage‐activated Ca 2+ currents. However, at higher concentrations 1–10 μ m AP interacts with ion channels or other membrane constituents to produce a variety of actions on both voltage and ligand gated ion channels.