Biomaterial Database

Pharmacology of voltage-gated and calcium-activated potassium channels. 1999

G J Kaczorowski, and M L Garcia

Department of Membrane Biochemistry and Biophysics, Merck Research Laboratories, PO Box 2000, 80N-31C, Rahway, NJ 07065, USA. gjk@merck.com

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.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002240	Carbohydrate Sequence	The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.	Carbohydrate Sequences,Sequence, Carbohydrate,Sequences, Carbohydrate
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014118	Toxins, Biological	Specific, characterizable, poisonous chemicals, often PROTEINS, with specific biological properties, including immunogenicity, produced by microbes, higher plants (PLANTS, TOXIC), or ANIMALS.	Biological Toxins
D015221	Potassium Channels	Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.	Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel
D015640	Ion Channel Gating	The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.	Gating, Ion Channel,Gatings, Ion Channel,Ion Channel Gatings
D017386	Sequence Homology, Amino Acid	The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.	Homologous Sequences, Amino Acid,Amino Acid Sequence Homology,Homologs, Amino Acid Sequence,Homologs, Protein Sequence,Homology, Protein Sequence,Protein Sequence Homologs,Protein Sequence Homology,Sequence Homology, Protein,Homolog, Protein Sequence,Homologies, Protein Sequence,Protein Sequence Homolog,Protein Sequence Homologies,Sequence Homolog, Protein,Sequence Homologies, Protein,Sequence Homologs, Protein
D026902	Potassium Channel Blockers	A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.	Channel Blockers, Potassium,Potassium Channel Blocker,Blocker, Potassium Channel,Blockers, Potassium Channel,Channel Blocker, Potassium