Analogies and differences in the mode of action and properties of binding sites (localization and mutual interactions) of two K + channel toxins, MCD peptide and dendrotoxin I

Abstract

Both the bee venom toxin, mast cell degranulating (MCD) peptide, and the snake toxin, dendrotoxin I (DTX I) induce epileptiform activity and paroxystic seizures after intracerebroventricular (i.c.v.) injection to rats. Although many of the properties of the two toxins, which are blockers of the same K + channel, appear to be very similar, a number of differences have been found. (1) Induced seizures have an hippocampal origin for MCD and two different origins, situated in the cortex and in the limbic system, for DTX I. (2) A first i.c.v. administration of DTX I desensitizes against a second ipsilateral injection of the same peptide as we had previously observed for MCD. However no cross-desensitization was observed between the two different toxins. (3) The number of high affinity (K d= 41 pM) binding sites for 125I-DTX I in synaptic membranes is about 5 times higher than the number of high affinity 125I-DTX I affinity (K d= 158 pM) binding sites for 125I-MCD. (4) Autoradiographic analysis of the distribution of high affinity binding sites has been compared to our previous analysis of high affinity 125I-MCD binding sites. High levels of high affinity binding sites for both toxins seem to be localized in synaps -rich areas. However high affinity binding sites for the two toxins are not always co-localized. Analysis of the mutual interactions between DTX I and MCD binding sites has revealed the presence of classes of low affinity binding sites for MCD. In most areas of the brain, a large proportion of high affinity binding sites for DTX I is allosterically related to low affinity binding for MCD.