CA2-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-cond uctance Ca2+-activated K+ (maxi-K) channels, the molecular identities of intermediate conductance Ca2+-activated K+ channels, including that of mature erythrocytes, remains unknown. We have used various peptide toxins to characterize the intermediate conductance Ca2+-activated K channels (Gardos pathway) of human and rabbit red cells. With studies on K+ transport and on binding of I-125-charybdotoxin (ChTX) and I-12 5-kaliotoxin (KTX) binding in red cells, we provide evidence for the d istinct nature of the red cell Gardos channel among described Ca2+-act ivated K+ channels based on (i) the characteristic inhibition and bind ing patterns produced by ChTX analogues, iberiotoxin (IbTX) and IbTX-l ike ChTX mutants, and KTX (1-37 and 1-38 variants); (ii) the presence of some properties heretofore attributed only to voltage-gated channel s, including inhibition of K transport by margatoxin (MgTX) and by sti chodactyla toxin (StK); (iii) and the ability of scyllatoxin (ScyTX) a nd apamin to displace bound I-125-charybdotoxin, a novel property for K+ channels. These unusual pharmacological characteristics suggest a u nique structure for the red cell Gardos channel.