COMPARABLE 30-KDA APAMIN BINDING POLYPEPTIDES MAY FULFILL EQUIVALENT ROLES WITHIN PUTATIVE SUBTYPES OF SMALL-CONDUCTANCE CA2-ACTIVATED K+ CHANNELS()

Apamin, a peptide neurotoxin from bee venom, blocks small conductance Ca2+-activated K+ channels in central synapses and peripheral tissues. Using I-125-apamin, single classes of high affinity binding sites (K- d 1-3 pM) were identified on plasma membranes from rat, rabbit, guinea pig, and bovine brain and from rabbit, guinea pig, and bovine liver. Binding was sensitive to scyllatoxin, dequalinium, gallamine, and d-tu bocurarine but not to charybdotoxin, toxin I, or mast cell degranulati ng peptide. In contrast, saturable binding of I-125-apamin to rat live r plasma membranes was virtually undetectable, thereby providing a cor relation with the ability to measure apamin-sensitive Ca2+-activated p otassium currents in rabbit and guinea pig hepatocytes but not in rat hepatocytes. In agreement with membrane binding studies, homobifunctio nal cross-linkers identified apparently identical 33-kDa I-125-apamin binding polypeptides on brain plasma membranes from all species and an alogous but distinct polypeptides on plasma membranes from rabbit, gui nea pig, and bovine liver. None of these affinity-labeled polypeptides were detectable on plasma membranes from rat liver. Affinity labeling was abolished on both liver and brain membranes by apamin, scyllatoxi n, dequalinium, gallamine, and d-tubocurarine. These results indicate that comparable similar to 30-kDa polypeptides may fulfill equivalent functional roles within putative subtypes of apamin-sensitive small co nductance Ca2+-activated K+ channels.