title: Actions of arginine polyamine on voltage and ligand-activated whole cell currents recorded from cultured neurones.
abstract: 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 Ca(2+)-dependent Cl- currents recorded from rat cultured dorsal root ganglion neurones were reversibly inhibited by arginine polyamine (AP; 0.001 to 100 microM). 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 microM 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 Ca(2+)-independent K+ current were more complex, 1 microM AP enhanced this current but 10 microM AP had a dual action, initially enhancing but then inhibiting the K+ current. 4. gamma-Aminobutyric acid-activated Cl- currents were also reversibly inhibited by 1 to 10 microM AP. In contrast N-methyl-D-aspartate currents recorded from rat cultured cerebellar neurones were greatly enhanced by 10 microM 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 microM AP interacts with ion channels or other membrane constituents to produce a variety of actions on both voltage and ligand gated ion channels.
authors.affiliation: Department of Physiology, St Georges Hospital Medical School, London.
authors.forename: R H
authors.initials: RH
authors.lastname: Scott
authors.forename: M I
authors.initials: MI
authors.lastname: Sweeney
authors.forename: E M
authors.initials: EM
authors.lastname: Kobrinsky
authors.forename: H A
authors.initials: HA
authors.lastname: Pearson
authors.forename: G H
authors.initials: GH
authors.lastname: Timms
authors.forename: I A
authors.initials: IA
authors.lastname: Pullar
authors.forename: S
authors.initials: S
authors.lastname: Wedley
authors.forename: A C
authors.initials: AC
authors.lastname: Dolphin
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D020960:omega-Conotoxins
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D010456:Peptides, Cyclic; D011073:Polyamines; C076245:arginine polyamine; D020960:omega-Conotoxins; C053423:Conus magus toxin; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D001120:Arginine; D011188:Potassium; D002118:Calcium