title: High-conductance calcium-activated potassium channels; structure, pharmacology, and function.
abstract: High-conductance calcium-activated potassium (maxi-K) channels comprise a specialized family of K+ channels. They are unique in their dual requirement for depolarization and Ca2+ binding for transition to the open, or conducting, state. Ion conduction through maxi-K channels is blocked by a family of venom-derived peptides, such as charybdotoxin and iberiotoxin. These peptides have been used to study function and structure of maxi-K channels, to identify novel channel modulators, and to follow the purification of functional maxi-K channels from smooth muscle. The channel consists of two dissimilar subunits, alpha and beta. The alpha subunit is a member of the slo Ca(2+)-activated K+ channel gene family and forms the ion conduction pore. The beta subunit is a structurally unique, membrane-spanning protein that contributes to channel gating and pharmacology. Potent, selective maxi-K channel effectors (both agonists and blockers) of low molecular weight have been identified from natural product sources. These agents, together with peptidyl inhibitors and site-directed antibodies raised against alpha and beta subunit sequences, can be used to anatomically map maxi-K channel expression, and to study the physiologic role of maxi-K channels in various tissues. One goal of such investigations is to determine whether maxi-K channels represent novel therapeutic targets.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Kaczorowski
authors.forename: H G
authors.initials: HG
authors.lastname: Knaus
authors.forename: R J
authors.initials: RJ
authors.lastname: Leonard
authors.forename: O B
authors.initials: OB
authors.lastname: McManus
authors.forename: M L
authors.initials: ML
authors.lastname: Garcia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018999:Charybdotoxin / Q000378:metabolism; D004224:Diterpenes / Q000378:metabolism; D006031:Glycosylation; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D014315:Triterpenes / Q000378:metabolism
chemical_list: D004224:Diterpenes; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms; D014315:Triterpenes; C104130:maxikdiol; D018999:Charybdotoxin; C064719:iberiotoxin