Ca2+-activated K+ channels of human and rabbit erythrocytes display distinctive patterns of inhibition by venom peptide toxins

Abstract

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.

SK4/IK1-like channels mediate TEA-insensitive, Ca2+-activated K+ currents in bovine parotid acinar cells

“…Figure 1B shows an example of the experiments demonstrating the absolute HCO 3 Ϫ /CO 2 requirement for ACh-induced net K ϩ efflux in bovine parotid fragments. The HCO 3 Ϫ /CO 2 dependency of the net K ϩ efflux in bovine parotid fragments was confirmed in experiments where the effect of removal of HCO 3 Ϫ /CO 2 from the perfusing solution was examined on A-23187-induced net K ϩ efflux (Fig. 1C).…”

“…These results collectively suggest that SK4/IK1-like channels mediate the native KCa currents in BPA cells. patch clamp; salivary secretion; HCO 3 Ϫ transport IT IS WELL ESTABLISHED that Ca 2ϩ -activated K ϩ (K Ca ) channels play a critical role in muscarinically stimulated fluid and electrolyte secretion in salivary glands (7). As in other secretory epithelia, the K ϩ channels in the basolateral membrane of acinar cells allow K ϩ to leave the cell and establish the apical (and basolateral) cell membrane potential more negative than the Nernst potential for anions such as Cl Ϫ and HCO 3 Ϫ , thereby providing a driving force for the sustained electrogenic anion efflux across the apical membrane.…”

Calmodulin Mediates Calcium-dependent Activation of the Intermediate Conductance KCa Channel,IKCa1

“…IK Ca channels, unlike SK Ca channels, are predominantly expressed in peripheral tissues, including those of the hematopoietic system, colon, lung, placenta, and pancreas (17)(18)(19)(20)(21)(22)(23). These channels have intermediate single channel conductance values of 11-40 pS and can be pharmacologically distinguished from SK Ca channels by their sensitivity to block by ChTX and clotrimazole and by their insensitivity to apamin (20,22).…”

Role of Ca2+-activated K+ channels and Na+,K+-ATPase in prostaglandin E1- and E2-induced inhibition of the adrenergic response in human vas deferens

“…These data indicate that K Ca 2 channels are not involved in the neuromodulatory effects of PGE 1 and PGE 2 . Charybdotoxin, a blocker of both K Ca 1.1 and K Ca 3.1 channels [22,23], prevented the inhibitory effects of PGE 1 and PGE 2 on sympathetic contractions of the human vas deferens. These results demonstrate that the K + channels involved are sensitive to…”