1 Fluoxetine (Prozac) is widely used as an antidepressant drug and is assumed to be a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (SSRI). Claims that its bene®cial psychotropic e ects extend beyond those in treatment of depression have drawn clinical and popular attention to this compound, raising the question of whether there is anything exceptional about the supposed selective actions. 2 We have used the voltage clamp technique to study the e ect of¯uoxetine on a neuronal, voltagedependent potassium (K + ) channel (RCK1; Kv1.1), expressed in Xenopus laevis oocytes. This channel subunit is abundantly expressed in the central nervous system and K + channels containing this subunit are involved in the repolarization process of many types of neurones. 3 Blockade of the K + currents by¯uoxetine was found to be use-and dose-dependent. Wash-out of this compound could not be achieved. Fluoxetine did not a ect the ion selectivity of this K + channel, as the reversal potential was unaltered. 4 Slowing of both activation and deactivation kinetics of the channel by¯uoxetine was observed, including tail current crossover upon repolarization. 5 Hodgkin-Huxley type of models and more generalized Markov chain models were used to ®t the kinetics of the data. Based upon a Markov kinetic scheme, our data can be interpreted to mean that blockade of¯uoxetine consists of two components: a voltage-independent occurring in the last closed, but available state of the channel, and a voltage-dependent occurring in the open state. 6 This study describes the ®rst biophysical working model for the mechanism of action of¯uoxetine on a neuronal, voltage-dependent K + channel, RCK1. Although this channel is not very potently blocked by¯uoxetine when expressed in oocytes, this study may help us to understand some of the clinical symptoms seen with elevated serum concentrations of this SSRI.

␣-Dendrotoxin, a 59-amino acid basic peptide from the venom of Dendroaspis angusticeps (green mamba snake), potently blocks some but not all voltage-dependent potassium channels. Here we have investigated the relative contribution of the individual ␣-subunits constituting functional Kv1.1 potassium channels to ␣-dendrotoxin binding. Three residues critical for ␣-dendrotoxin binding and located in the loop between domains S5 and S6 were mutated (A352P, E353S, and Y379H), and multimeric cDNAs were constructed encoding homoand heterotetrameric channels composed of all possible ratios of wild-type and mutant ␣-subunits. Complete mutant channels were about 200-fold less sensitive for the ␣-dendrotoxin block than complete wild-type channels, which is attributable to a smaller association rate. Analysis of the bimolecular reaction between ␣-dendrotoxin and the different homo-and heteromeric channel constructs revealed that the association rate depends on the number of wild-type ␣-subunits in the functional channel. Furthermore, we observed a linear relationship between the number of wild-type ␣-subunits in functional channels and the free energy for ␣-dendrotoxin binding, providing evidence that all four ␣-subunits must interact with ␣-dendrotoxin to produce a high affinity binding site.

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Assessment of the acrylamide intake of the Belgian population and the effect of mitigation strategies. Food Additives and Contaminants, 2010, 27 (09), pp.1199-1207. <10.1080/19440049.2010 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59

A disulfide-rich, low-molecular-mass toxin-like peptide has been isolated from Parabuthus schlechteri venom using gel filtration, ion exchange, and reversed phase chromatography. Partial characterization of this peptide reveals a relationship with four-disulfide bridge proteins belonging to the family of short' insectotoxins (44% residue identity). In recognition hereof, the peptide was named PBITx1 (sITx10). Our work also reports on the deduced sequences of two other`short' insectotoxins from Buthus eupeus, I Q and I R , and it provides a consensus sequence and nomenclature for all known`short' insectotoxins. Finally, sequence similarities with K + channel blockers (charybdotoxin, U U-conotoxin), and a Cl 3 channel blocker (chlorotoxin) are highlighted.z 1998 Federation of European Biochemical Societies.

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