gamma 1- and gamma 2-zeathionins (gamma 1-Z and gamma 2-Z) are members of a family of small and basic peptides involved in plant protection. These plant defensins exhibit remarkable structural similarity to scorpion neurotoxins and insect defensins, In the present report, we used the whole-cell patch clamp technique to investigate the inhibition of the sodium current (I-Na) by gamma 1-Z and gamma 2-Z in the GH3 cell line, Both gamma 1-Z and gamma 2-Z rapidly and reversibly inhibited IN, without changing the kinetics or voltage dependence of activation or inactivation. To our knowledge, this is the first example of a plant protein that inhibits the sodium channel. From structural comparisons with the mu-conotoxins, a family of peptides that block the sodium channel, we detected some similar features that could provide the basis of inhibition of sodium channels by gamma-zeathionins. (C) 1998 Federation of European Biochemical Societies.