Diffusion-controlled binding of a peptide neurotoxin to its K+ channel receptor.
Single Ca2(+)-activated K+ channels were reconstituted into planar lipid bilayer membranes, and the effect of charybdotoxin, a pore-blocking peptide from scorpion venom, was studied. In particular, the effect of solution viscosity on the kinetics of block was assessed in order to test the idea that toxin binding is diffusion-controlled. This idea is supported by the strictly inverse relation between solution viscosity and the rate constants of both association and dissociation of peptide with the K+ channel mouth. However, at an ionic strength high enough to suppress local electrostatic potentials, the diffusion-controlled on-rate constant is surprisingly low, 10(5) M-1 s-1. These slow, viscosity-dependent kinetics may be understood if charybdotoxin can attain the bound state only from a rare set of encounters with the K+ channel.
Miller
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Howard Hughes Medical Institute, Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000502:physiology; D018999:Charybdotoxin; D004058:Diffusion; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012604:Scorpion Venoms / Q000378:metabolism* / Q000494:pharmacology; D014783:Viscosity
D008051:Lipid Bilayers; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D002118:Calcium