Ca(2+)-activated K+ channels of human and rabbit erythrocytes display distinctive patterns of inhibition by venom peptide toxins.
Despite recent progress in the molecular characterization of high-conductance Ca(2+)-activated K+ (maxi-K) channels, the molecular identities of intermediate conductance Ca(2+)-activated K+ channels, including that of mature erythrocytes, remains unknown. We have used various peptide toxins to characterize the intermediate conductance Ca(2+)-activated K+ channels (Gardos pathway) of human and rabbit red cells. With studies on K+ transport and on binding of 125I-charybdotoxin (ChTX) and 125I-kaliotoxin (KTX) binding in red cells, we provide evidence for the distinct nature of the red cell Gardos channel among described Ca(2+)-activated K+ channels based on (i) the characteristic inhibition and binding patterns produced by ChTX analogues, iberiotoxin (IbTX) and IbTX-like ChTX mutants, and KTX (1-37 and 1-38 variants); (ii) the presence of some properties heretofore attributed only to voltage-gated channels, including inhibition of K transport by margatoxin (MgTX) and by stichodactyla toxin (StK); (iii) and the ability of scyllatoxin (ScyTX) and apamin to displace bound 125I-charybdotoxin, a novel property for K+ channels. These unusual pharmacological characteristics suggest a unique structure for the red cell Gardos channel.
Brugnara
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Departments of Pathology and Laboratory Medicine, Children's Hospital, Boston, MA 02115, USA.
Armsby
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CC
De Franceschi
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L
Crest
M
M
Euclaire
M F
MF
Alper
S L
SL
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018999:Charybdotoxin / Q000235:genetics / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D009498:Neurotoxins / Q000633:toxicity; D010455:Peptides / Q000633:toxicity*; D017354:Point Mutation; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits; D012413:Rubidium / Q000378:metabolism; D012604:Scorpion Venoms / Q000633:toxicity*
D009498:Neurotoxins; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; C072276:kaliotoxin; D018999:Charybdotoxin; C056574:leiurotoxin I; C077910:margatoxin; C064719:iberiotoxin; D012413:Rubidium; D011188:Potassium; D002118:Calcium