Use of toxins to study potassium channels.
Potassium channels comprise groups of diverse proteins which can be distinguished according to each member's biophysical properties. Some types of K+ channels are blocked with high affinity by specific peptidyl toxins. Three toxins, charybdotoxin, iberiotoxin, and noxiustoxin, which display a high degree of homology in their primary amino acid sequences, have been purified to homogeneity from scorpion venom. While charybdotoxin and noxiustoxin are known to inhibit more than one class of channel (i.e., several Ca(2+)-activated and voltage-dependent K+ channels), iberiotoxin appears to be a selective blocker of the high-conductance, Ca(2+)-activated K+ channel that is present in muscle and neuroendocrine tissue. A distinct class of small-conductance Ca(2+)-activated K+ channel is blocked by two other toxins, apamin and leiurotoxin-1, that share no sequence homology with each other. A family of homologous toxins, the dendrotoxins, have been purified from venom of various related species of snakes. These toxins inhibit several inactivating voltage-dependent K+ channels. Although molecular biology approaches have been employed to identify and characterize several species of voltage-gated K+ channels, toxins directed against a particular channel can still be useful in defining the physiological role of that channel in a particular tissue. In addition, for those K+ channels which are not yet successfully probed by molecular biology techniques, toxins can be used as biochemical tools with which to purify the target protein of interest.
Garcia
M L
ML
Department of Membrane Biochemistry and Biophysics, Merck Institute for Therapeutic Research, Rahway, New Jersey 07065.
Galvez
A
A
Garcia-Calvo
M
M
King
V F
VF
Vazquez
J
J
Kaczorowski
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology*
D015221:Potassium Channels; D014118:Toxins, Biological