Structural basis of voltage-gated K+ channel pharmacology.
Major advances have been made in understanding the domains and amino acid sidechains important for the function of voltage-gated K+ channels, by combining recombinant DNA techniques with pharmacological and electrophysiological approaches. As explained in this review by Olaf Pongs, the results of these experiments have enabled description of a detailed model of the K+ channel pore structure and provide an exciting picture of how open-channel blockers occlude the pore of K+ channels. Since the pore is a highly conserved structure among voltage-gated K+ channels, there are only limited possibilities for open K+ channel blockers to distinguish between the many distinct voltage-gated K+ channels, which have diverse kinetic and conductance properties.
Pongs
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Zentrum für Molekulare Neurobiologie, Universität Hamburg, FRG.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018999:Charybdotoxin; D003001:Cloning, Molecular; D004546:Elapid Venoms / Q000378:metabolism / Q000494:pharmacology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012604:Scorpion Venoms / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism / Q000494:pharmacology*
D004546:Elapid Venoms; D009498:Neurotoxins; D015221:Potassium Channels; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D019789:Tetraethylammonium; C020273:dendrotoxin