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 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.
Scott
R H
RH
Department of Physiology, St Georges Hospital Medical School, London.
Sweeney
M I
MI
Kobrinsky
E M
EM
Pearson
H A
HA
Timms
G H
GH
Pullar
I A
IA
Wedley
S
S
Dolphin
A C
AC
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
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