Journal of Bioenergetics and Biomembranes

, Volume 28, Issue 3, pp 255–267

High-conductance calcium-activated potassium channels; Structure, pharmacology, and function

  • Gregory J. Kaczorowski
  • Hans -Günther Knaus
  • Reid J. Leonard
  • Owen B. McManus
  • Maria L. Garcia
Article

DOI: 10.1007/BF02110699

Cite this article as:
Kaczorowski, G.J., Knaus, H.-., Leonard, R.J. et al. J Bioenerg Biomembr (1996) 28: 255. doi:10.1007/BF02110699

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, α and Β. The α subunit is a member of theslo Ca2+-activated K+ channel gene family and forms the ion conduction pore. The Β 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 α and Β 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.

Key words

maxi-K channelscharybdotoxiniberiotoxinsmooth muscleion channel purificationslo channelsΒ-subunitK channel agonistsK channel blockersion channel pharmacology

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Gregory J. Kaczorowski
    • 1
  • Hans -Günther Knaus
    • 2
  • Reid J. Leonard
    • 1
  • Owen B. McManus
    • 1
  • Maria L. Garcia
    • 1
  1. 1.Merck Research LaboratoriesRahway
  2. 2.Institute for Biochemical PharmacologyUniversity of InnsbruckInnsbruckAustria