The apamin-sensitive Ca2+-dependent K+ channel molecular properties, differentiation and endogenous ligands in mammalian brain.
Apamin is a bee venom neurotoxin of 10 amino acids containing two disulphide bridges. Current-clamp and voltage-clamp experiments have shown that apamin externally applied blocks specifically at low concentration (0.1 microM) the Ca2+-dependent slow K+ conductance which mediates the long-lasting after-hyperpolarization in neuroblastoma cells and rat muscle cells in culture. The apamin-sensitive Ca2+-dependent slow K+ conductance is voltage-dependent and tetraethylamonium-insensitive. It is distinct from the high conductance Ca+-dependent K+ channel revealed by patch-clamp experiments. Biochemical characterization of the apamin receptor in rat striated muscle, neuroblastoma cells, rat synaptosomes, smooth muscles and hepatocytes was carried out with the use of a radiolabelled monoiodo-apamin derivative (125I-apamin) of high specific radioactivity (2000 Ci/mmol). The dissociation constant of the apamin-receptor complex is between 15 and 60 pM for all tissue preparations. The density of binding sites is very low: between 1 and 40 fmol/mg of protein. Radiation-inactivation analysis indicates a molecular mass for the apamin receptor of 250 000 Da whereas affinity labelling with 125I-apamin results in covalent labelling of a single polypeptide chain with a molecular mass of about 30 000 Da. Autoradiography of 125I-apamin binding sites reveals the presence of Ca2+-activated K+ channels in many regions of the brain. There is an all-or-none control of the expression of the apamin-sensitive Ca2+-dependent K+ channel by innervation in mammalian skeletal muscle. There exists an endogenous equivalent of apamin in rat brain.
D000200:Action Potentials; D000818:Animals; D001030:Apamin / Q000378:metabolism*; D001514:Bee Venoms / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D007473:Ion Channels; D008564:Membrane Potentials; D008970:Molecular Weight; D010455:Peptides / Q000032:analysis; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000032:analysis; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001514:Bee Venoms; D007473:Ion Channels; D010455:Peptides; D015221:Potassium Channels; D017981:Receptors, Neurotransmitter; D013757:Tetraethylammonium Compounds; C033799:apamin receptor; D001030:Apamin; D011188:Potassium; D002118:Calcium