Competition for block of a Ca2(+)-activated K+ channel by charybdotoxin and tetraethylammonium.
Single high-conductance Ca2(+)-activated K+ channels were incorporated into planar lipid bilayers, and the discrete block by charybdotoxin (CTX), a protein inhibitor of this channel, was studied. In particular, the effect of externally added tetraethylammonium (TEA) on CTX blocking kinetics was investigated. TEA decreases the on-rate of CTX in exact proportion to its blocking of the single-channel current. The CTX off-rate is unaffected by TEA. The results demonstrate that TEA and CTX are mutually exclusive in their binding to the channel. Since the site of TEA binding is known to be located on the external side of the conduction pore, this result further strengthens the proposal that the CTX binding site is located in the external mouth of the channel.
Miller
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Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D018999:Charybdotoxin; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000648:ultrastructure; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D015221:Potassium Channels; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D011188:Potassium; D002118:Calcium