Pharmacology of voltage-gated and calcium-activated potassium channels.
Several important new findings have furthered the development of voltage-gated and calcium-activated potassium channel pharmacology. The molecular constituents of several members of these large ion channel families were identified. Small-molecule modulators of some of these channels were reported, including correolide, the first potent, small-molecule, natural product inhibitor of the Shaker family of voltage-gated potassium channels to be disclosed. The initial crystal structure of a bacterial potassium channel was determined; this work gives a physical basis for understanding the mechanisms of ion selectivity and ion conduction. With the recent molecular characterization of a potassium channel structure and the discovery of new templates for channel modulatory agents, the ability to rationally identify and develop potassium channel agonists and antagonists may become a reality in the near future.
Department of Membrane Biochemistry and Biophysics, Merck Research Laboratories, PO Box 2000, 80N-31C, Rahway, NJ 07065, USA. gjk@merck.com
G J
GJ
Kaczorowski
M L
ML
Garcia
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014118:Toxins, Biological / Q000737:chemistry / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014118:Toxins, Biological; D002118:Calcium