Probing a Ca2+-activated K+ channel with quaternary ammonium ions

Alfredo Villarroel, Osvaldo Alvarez, Andres Oberhauser, Ramon Latorre

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

A series of quaternary amonium (QA) ions were used to probe the gross architecture of the ion conduction pathway in a Ca2+-activated K+ channel from rat muscle membrane. The channels were inserted into planar phospholipid membranes and the single channel currents were measured in the presence of the different QA ions. Internally applied monovalent QA ions (e.g. tetramethylammonium and analogues) induced a voltage-dependent blockade with a unique effective valence of the block equal to 0.30, and blocking potency increases as the compound is made more hydrophobic. Blockade is relieved by increasing the K+ concentration of the internal or external side of the channel. The effective valence of block is independent of K+ concentration. These results suggest that, from the internal side, all monovalent QA ions interact with a site located in the channel conduction system. Divalent QA ions of the type n-alkylbis-α,β-trimethylammonium (bisQn) applied internally also block the channel in a voltage dependent fashion. For short chains (bisQ2-bisQ5), the effective valence decreases with chain length from 0.41 to 0.27, it remains constant for bisQ5 to bisQ6 and increases up to 0.54 for bisQ10. This dependence of block with chain length implies that 27% of the voltage drop within the channel occurs over a distance of ≈ 1 nm. Externally applied monovalent QA ions also block the channel. The site is specific for tetraethylammonium; increasing or decreasing the side chains in one methylene group decrease potency by about 400-fold. It is concluded that the Ca2+-activated K+ channel has wide mouths located at each end and that they are different in molecular nature.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalPflügers Archiv European Journal of Physiology
Volume413
Issue number2
DOIs
StatePublished - Dec 1988
Externally publishedYes

Fingerprint

Calcium-Activated Potassium Channels
Ammonium Compounds
Ions
Chain length
Membranes
Tetraethylammonium
Electric potential
Ion Channels
Muscle
Mouth
Rats
Phospholipids
Muscles

Keywords

  • Blockade
  • Ca-activated K channel
  • Lipid bilayers
  • Quaternary ammonium ions

ASJC Scopus subject areas

  • Physiology

Cite this

Probing a Ca2+-activated K+ channel with quaternary ammonium ions. / Villarroel, Alfredo; Alvarez, Osvaldo; Oberhauser, Andres; Latorre, Ramon.

In: Pflügers Archiv European Journal of Physiology, Vol. 413, No. 2, 12.1988, p. 118-126.

Research output: Contribution to journalArticle

Villarroel, Alfredo ; Alvarez, Osvaldo ; Oberhauser, Andres ; Latorre, Ramon. / Probing a Ca2+-activated K+ channel with quaternary ammonium ions. In: Pflügers Archiv European Journal of Physiology. 1988 ; Vol. 413, No. 2. pp. 118-126.
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