Distribution in rat brain of binding sites of kaliotoxin, a blocker of Kv1.1 and Kv1.3 alpha-subunits

The distribution of the binding sites for kaliotoxin (KTX), a blocker of vo ltage-dependent K+ channels, was studied with quantitative autoradiography in adult rat brain and during postnatal brain maturation. Iodinated KTX bou nd 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 hig hest densities were found in the neocortex, hypothalamus, dentate gyrus, be d nucleus of the stria terminalis, and parabrachial nuclei. The lowest leve l was observed in the white matter. From postnatal day 5 onward, KTX bindin g sites were detectable only in the hindbrain. The density of KTX binding s ites in whole brain drastically increased after postnatal day 15 to achieve adult levels at postnatal day 60 in the whole brain. Bath application of K TX to Xenopus laevis oocytes blocked recombinant Kv1.3 and Kv1.1 channels p otently 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 ma mmalian 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.