Block of maurotoxin and charybdotoxin on human intermediate-conductance calcium-activated potassium channels (hIKCa1)

Abstract

Using human intermediate-conductance calcium-activated potassium (hIKCa1) channels as a model we aimed to characterize structural differences between maurotoxin (MTX) and charybdotoxin (CTX) and to gain new insights into the molecular determinants that define the interaction of these pore-blocking peptides with hIKCa1 channel. We report here that the block of MTX, but not of CTX on current through hIKCa1 channels is pH 0 dependent. The replacement of histidine 236 from hIKCa1 channel with a smaller amino acid, cystein, did not change MTX binding affinity, however, partially affected the pH 0 dependency of its block at low pH 0. In contrast, CTX binding affinity to the hIKCa1_H236C channel mutant was increased suggesting that His236 might play a role in the binding of CTX, but has only a weak influence in the binding of MTX to hIKCa1 channels.