Suramin protects the murine motor nerves from the toxic effects of presynaptic Ca2+ channel inhibitors

The purpose of this study is to investigate whether suramin is capable of p reventing the neurotoxic effects of Ca2+ channel inhibitors at the presynap tic sites. Mouse diaphragm and triangularis sterni preparations were used f or this study in order to measure the muscle tension and nerve terminal Ca2 + current, respectively. Both omega-conotoxin MVIIC and omega-agatoxin IVA markedly inhibit the nerve-evoked muscle contractions as well as the nerve terminal Ca2+ current respectively. Pretreatment with suramin (0.3 mM) sign ificantly reduced the inhibitory effect of nerve-evoked muscle contractions and Ca2+ current induced by either omega-conotoxin MVIIC or omega-agatoxin IVA but not that induced by the non-selective Ca2+ channel blocker, Cd2+. Neither suramin nor Ca2+-channel toxins significantly affect Na+- and K+ cu rrents of the nerve terminals. These findings indicate that suramin selecti vely interferes the action of presynaptic Ca2+ channel neurotoxins and thus reduces their depressant effects on the muscle contractions. The implicati on of these findings is that suramin and its derivatives may potentially be come useful agents in management of intoxication of Ca2+ channel neurotoxin s. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.