Block of maurotoxin and charybdotoxin on human intermediate-conductance calcium-activated potassium channels (hIKCa1).
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 pH0 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 pH0 dependency of its block at low pH0. 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.
Visan
Violeta
V
Department of Applied Physiology, University of Ulm, Albert-Einstein-Allee 11, Ulm 89081, Germany.
Sabatier
Jean-Marc
JM
Grissmer
Stephan
S
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D018999:Charybdotoxin / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D026902:Potassium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D011485:Protein Binding / Q000187:drug effects; D012604:Scorpion Venoms / Q000378:metabolism / Q000494:pharmacology*; D012605:Scorpions / Q000737:chemistry*; D016415:Sequence Alignment; D014162:Transfection
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms; C104498:maurotoxin; D018999:Charybdotoxin