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  • Title: Comparison of the distribution of binding sites for the potassium channel ligands [125I]apamin, [125I]charybdotoxin and [125I]iodoglyburide in the rat brain.
    Author: Gehlert DR, Gackenheimer SL.
    Journal: Neuroscience; 1993 Jan; 52(1):191-205. PubMed ID: 7679479.
    Abstract:
    Potassium channels represent a diverse and promising target for drug development. Pharmacological subtypes of K channels have begun to emerge based on the development of both organic molecules and peptide toxins which possess subtype selectivity. In order to evaluate the neuroanatomical distribution of these subtypes we have utilized the ligands [125I]apamin, [125I]charybdotoxin and [125I]iodoglyburide in an autoradiographic study of rat brain. In the rat brain, these ligands have selectivity for the low conductance Ca(2+)-activated, voltage-gated K channels and ATP-sensitive K channels respectively. The distribution of binding sites for these three ligands were distinctly different. [125I]Apamin binding was highest in various thalamic and hippocampal structures, while only low to moderate levels of [125I]charybdotoxin binding were seen in these regions. In contrast, very high levels of [125I]charbydotoxin were seen in white matter regions such as the lateral olfactory tract and fasciculus retroflexus. High levels of [125I]charybdotoxin binding were also seen in gray matter-containing regions such as the zona incerta, medial geniculate and superior colliculus, where low to moderate [125I]apamin binding was found. [125I]Iodoglyburide presented a more uniform binding with the highest levels in the globus pallidus, islands of Calleja, anteroventral nucleus of the thalamus and zonas reticulata of the substantia nigra. These results indicate that subtypes of K channels have very different distributions in the brain. As such, the results imply differing CNS actions for potential modulators of K channel subtypes.
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