Title: High-conductance calcium-activated potassium channels; structure, pharmacology, and function.

Authors: G J Kaczorowski, H G Knaus, R J Leonard, O B McManus, M L Garcia

Journal, date & volume: J. Bioenerg. Biomembr., 1996 Jun , 28, 255-67

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/8807400

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.