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Kv4 channels sensitive to BmTX3 in rat nervous system: autoradiographic analysis of their distribution during brain ontogenesis.

Helene Vacher, Sylvie Diochot, Pierre E Bougis, Marie-France Martin-Eauclaire, Christiane Mourre

Eur. J. Neurosci., 2006 Sep , 24, 1325-40

The binding site distribution of sBmTX3, a chemically synthesized toxin originally purified from the venom of the scorpion Buthus martensi, was investigated in adult and developing rat brain, using patch-clamp experiments and quantitative autoradiography. The molecular basis of these sBmTX3 sites was analysed by electrophysiology on transient Kv currents recorded in mammalian transfected cells. The rapidly activating and inactivating Kv4.1 current was inhibited by sBmTX3 (IC50, 105 nM). The inhibition was less effective on Kv4.2 and Kv4.3 channels and the toxin did not affect other transient currents such as Kv1.4 and Kv3.4. The distribution of the 125I-sBmTX3 binding sites was heterogeneous, with a 113-fold difference between the highest and the lowest densities in adult rat brain. The site density was particularly important in the caudate-putamen and accumbens nucleus, thalamus, hippocampal formation and cerebellum. The affinity of sBmTX3 remained constant during brain ontogenesis. The level of sBmTX3 binding sites was very low in prenatal and postnatal stages to postnatal day (P)12 but drastically increased from P15 in the major part of the studied structures except in the CA3 hippocampal field where the density was very high from P6. Thus, the distribution of sBmTX3 binding sites in rat brain and its electrophysiological characteristics suggest that sBmTX3 specifically binds to the Kv4 subfamily of K channels.