Mapping of Maurotoxin Binding Sites on hKv1.2, hKv1.3, and hIKCa1 Channels

Maurotoxin (MTX) is a potent blocker of human voltage-acti-vated Kv1.2 and intermediate-conductance calcium-activated potassium channels, hIKCa1. Because its blocking affinity on both channels is similar, although the pore region of these channels show only few conserved amino acids, we aimed to characterize the binding sites of MTX in these channels. Inves-tigating the pHo dependence of MTX block on current through hKv1.2 channels, we concluded that the block is less pHo-sensitive than for hIKCa1 channels. Using mutant cycle analysis and computer docking, we tried to identify the amino acids through which MTX binds to hKv1.2 and hIKCa1 channels. We report that MTX interacts with hKv1.2 mainly through six strong interactions. Lys23 from MTX protrudes into the channel pore interacting with the GYGD motif, whereas Tyr32 and Lys7 inter