Inhibitory actions of synthesised polyamine spider toxins and their analogues on Ca 2+-activated Cl − currents recorded from cultured DRG neurones from neonatal rats

• Published in: Neuroscience letters Vol. 251; no. 2; pp. 117 - 120
• Main Authors: Sutton, Kathy G, Stapleton, Simon R, Scott, Roderick H
• Format: Journal Article
• Language: English
• Published: Elsevier Ireland Ltd 1998
• Subjects: Argiotoxin-636; Calcium-activated chloride currents; DM-Nitrophen; Intracellular flash photolysis; Polyamine toxins; Synthesised FTX; DM-Nitrophen; Calcium-activated chloride currents; Synthesised FTX; Argiotoxin-636; Polyamine toxins; Intracellular flash photolysis
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(98)00524-2

The whole cell variant of the patch clamp technique was used to investigate the actions of polyamine spider toxins and their analogues on high voltage-activated Ca 2+ currents and Ca 2+-activated Cl − currents ( I Cl(Ca)). The actions of synthesised FTX (putative natural toxin from the American funnel web spider), sFTX-3.3, Orn-FTX-3.3, Lys-FTX-3.3, and argiotoxin-636 on cultured dorsal root ganglion neurones from neonatal rats were investigated. Synthesised FTX (1 μM) inhibited I Cl(Ca) but did not inhibit high voltage-activated Ca 2+ currents. In contrast, sFTX-3.3 (10 μM) inhibited both high voltage-activated Ca 2+ currents and the associated I Cl(Ca) in near equal proportions. Argiotoxin-636 (1–10 μM) inhibited I Cl(Ca) evoked by Ca 2+ entry through voltage-activated channels and by intracellular photorelease of Ca 2+ from a caged precursor DM-nitrophen. This data indicates that synthesised FTX and argiotoxin-636 directly inhibit Ca 2+-activated Cl − channels. In conclusion, the potency of polyamines as non-selective inhibitors of Ca 2+ channels and Ca 2+-activated Cl − channels is in part determined by the presence of a terminal arginine and this may involve an interaction between terminal guanidino groups and Ca 2+ binding sites.