title: Distribution in rat brain of binding sites of kaliotoxin, a blocker of Kv1.1 and Kv1.3 alpha-subunits.
abstract: The distribution of the binding sites for kaliotoxin (KTX), a blocker of voltage-dependent K(+) channels, was studied with quantitative autoradiography in adult rat brain and during postnatal brain maturation. Iodinated KTX bound specifically to tissue sections with a high affinity (K(d) = 82 pM) and a maximal binding capacity of 13.4 fmol/mg protein. The distribution of KTX binding sites within the central nervous system was heterogeneous. The highest densities were found in the neocortex, hypothalamus, dentate gyrus, bed nucleus of the stria terminalis, and parabrachial nuclei. The lowest level was observed in the white matter. From postnatal day 5 onward, KTX binding sites were detectable only in the hindbrain. The density of KTX binding sites in whole brain drastically increased after postnatal day 15 to achieve adult levels at postnatal day 60 in the whole brain. Bath application of KTX to Xenopus laevis oocytes blocked recombinant Kv1.3 and Kv1.1 channels potently and Kv1.2 channels less potently, with respective K(d) values of 0.1, 1.5, and 25 nM. KTX affinities for each of these channels expressed in mammalian cells were about 10-fold lower. A comparison of the distribution of KTX binding sites with that of Kv1 channel polypeptides, together with the pharmacology of KTX block, suggests that the principal targets for KTX in rat brain are K(+) channels containing Kv1.1 and Kv1.3 alpha-subunits.
authors.affiliation: Laboratoire de Neurobiologie Intégrative et Adaptative, Centre National de la Recherche Scientifique-Université de Provence, Marseille, France. mourre@newsup.univ-mrs.fr
authors.forename: C
authors.initials: C
authors.lastname: Mourre
authors.forename: M N
authors.initials: MN
authors.lastname: Chernova
authors.forename: M F
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.forename: R
authors.initials: R
authors.lastname: Bessone
authors.forename: G
authors.initials: G
authors.lastname: Jacquet
authors.forename: M
authors.initials: M
authors.lastname: Gola
authors.forename: S L
authors.initials: SL
authors.lastname: Alper
authors.forename: M
authors.initials: M
authors.lastname: Crest
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology* / Q000254:growth & development; D001923:Brain Chemistry / Q000502:physiology*; D002460:Cell Line; D004558:Electric Stimulation; D004594:Electrophysiology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051662:Kv1.1 Potassium Channel; D051663:Kv1.2 Potassium Channel; D051664:Kv1.3 Potassium Channel; D008297:Male; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: C496946:KCNA1 protein, human; C496969:KCNA2 protein, human; C496973:KCNA3 protein, human; C496947:Kcna1 protein, mouse; C496970:Kcna2 protein, mouse; C496972:Kcna2 protein, rat; C496974:Kcna3 protein, mouse; C496975:Kcna3 protein, rat; D051663:Kv1.2 Potassium Channel; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; C072276:kaliotoxin; D051662:Kv1.1 Potassium Channel