The Nhe enterotoxin was discovered following a large food-poisoning outbreak in Norway in 1995, and consists of three separate proteins: Nhe-A, - B, and -C. The Nhe complex induces cell lysis in clonal epithelial cell lines (Vero and Caco2), and forms channels of 200­700 pS conductance in planar lipid bilayers (Fagerlund et al. 2008). Electrophysiological effects of Nhe on cell membranes have previously not been examined. We have studied the membrane effects of Nhe on Vero cells and clonal pituitary cells (GH₄ cells) by patch clamp recordings and microfluorometric (fura-2) monitoring of the cytosolic Ca²⁺ level ([Ca²⁺] _i) and fluorochrome concentration. Cell lysis was assessed by measuring the release of lactate dehydrogenase (LDH). Within 30 min, preparations of Nhe from 5 hr culture supernatants of B. cereus NVH75/95 induced massive LDH release, i.e., 90­100 % of maximum (triton X-100) in both cell types. Whole-cell voltage clamp recordings revealed Nhe-induced insertion of gigantic channels after a delay of 1- 3 min. The mean single channel conductance was estimated to 8 nS, which is more than 10 times the mean channel conductance in planar lipid bilayers. The reversal potential of the channel currents was close to 0 mV, indicating an unselective channel. To our knowledge, this is the highest channel conductance reported in cell membranes under quasi-physiological conditions. Nhe also increased [Ca²⁺]_i abruptly to saturating levels after a similar delay, followed by a gradual loss of fluorochrome from the cytosol. We conclude that the Nhe toxin complex induces cell lysis by forming large conductance channels in the plasma membrane of target epithelia. Reference: Fagerlund A., Lindbäck T., Storset A.K., Granum P.E. and Hardy S.P. 2008. Microbiology 154, 693–704.