INHIBITORY ACTIONS OF SYNTHESIZED POLYAMINE SPIDER TOXINS AND THEIR ANALOGS ON CA2-ACTIVATED CL- CURRENTS RECORDED FROM CULTURED DRG NEURONS FROM NEONATAL RATS()

The whole cell variant of the patch clamp technique was used to invest igate the actions of polyamine spider toxins and their analogues on hi gh voltage-activated Ca2+ currents and Ca2+-activated Cl- currents (I- CI(Ca)). The actions of synthesised FTX (putative natural toxin from t he American funnel web spider), sFTX-3.3, Orn-FTX-3.3, Lys-FTX-3.3, an d argiotoxin-636 on cultured dorsal root ganglion neurones from neonat al rats were investigated. Synthesised FTX (1 mu M) inhibited I-CI(Ca) but did not inhibit high voltage-activated Ca2+ currents. In contrast , sFTX-3.3 (10 mu M) inhibited both high voltage-activated currents an d the associated I-CI(Ca) in near equal proportions. Argiotoxin-636 (1 -10 mu M) inhibited I-CI(Ca) evoked by Ca2+ entry through voltage-acti vated channels and by intracellular photorelease of Ca2+ from a caged precursor DM-nitrophen. This data indicates that synthesised FTX and a rgiotoxin-636 directly inhibit Ca2+-activated Cl- channels. In conclus ion, the potency of polyamines as non-selective inhibitors of Ca2+ cha nnels and Ca2+-activated Cl- channels is in part determined by the pre sence of a terminal arginine and this may involve an interaction betwe en terminal guanidino groups and Ca2+ binding sites. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.