EFFECT OF ALKALOID TOXINS FROM TROPICAL MARINE SPONGES ON MEMBRANE SODIUM CURRENTS

Dibromosceptrin and clathrodin are alkaloid compounds purified from tr opical marine sponges of the genus Agelas. Experiments done using the whole cell configuration of the patch clamp technique revealed that th ese compounds have neurotoxic activity. Both compounds decreased by 27 -40% the average maximum amplitudes of pharmacologically isolated inwa rd sodium currents in cells isolated from chick embryo sympathetic gan glia. Current-voltage data, fitted using Boltzmann's equation, did not show any effect of these agents on the voltage dependence of current activation. However, the voltage dependence of current inactivation wa s shifted toward more negative potentials by dibromosceptrin, changing by an average of 20 mV the voltage for 50% inactivation, In contrast, clathrodin shifted this voltage dependence of inactivation toward mor e positive potentials and changed the voltage for 50% inactivation by 14 mV. Time for current reactivation was not altered by clathrodin but was slightly prolonged by dibromosceptrin. Similarly, dibromosceptrin was more effective than clathrodin in delaying the time course of cur rent decay. Thus, these two alkaloids appear to be new sodium channel neurotoxins acting through different mechanisms, dibromosceptrin modif ying the channel inactivation characteristics and clathrodin probably influencing channel ionic conductance.