Aminoglycoside blockade of Ca2+-activated K+ channel from rat brain synaptosomal membranes incorporated into planar bilayers

Kazushi Nomura, Keiji Naruse, Kazuyoshi Watanabe, Masahiro Sokabe

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Ca2+-activated K+ channels from rat brain synaptosomal membranes were incorporated into planar lipid bilayers, and the effects of aminoglycoside antibiotics on the single channel conductance (258±13 pS at 100 mm K+) were investigated. Aminoglycosides reduced the single channel conductance from the 'cis' (cytoplasmic) side in a dose- and voltage-dependent manner. Voltage dependence of the blockade indicated an interaction between positively charged amino residues of aminoglycoside antibiotics and a binding site located within the electric field of the ion-conducting pathway. The order of blocking potency was consistent with that of the number of amino residues of aminoglycosides (neomycin (6)>dibekacin (5)>ribostamycin (4)=kanamycin (4)), while the electrical distance (zδ=0.46-0.49) of the binding site kept almost constant for each drug. These zδs were almost the same with those (0.46-0.51) of alkyldiamine blockers with two amino residues (total net charge of +2) and approximately twice of those (0.25-0.26) of alkylmonoamine blockers (total net charge of +1). Assuming that amino residues of aminoglycosides and alkylamines shared the same binding site located at 25% voltage drop from the cytoplasmic surface of the channel, the site would have to be at least large enough to accommodate one diamino sugar residue of the aminoglycoside in order to simultaneously interact with two positively charged amino groups. Dose- and voltage-dependent blockade of the channel by gallamine, an extremely bulky trivalent organic cation, supported the picture that the channel has a wide mouth on the cytoplasmic side and its 'pore' region, where voltage drop occurs, may also be quite wide and nonselective, suddenly tapering to a constriction where most charged cations block the channel by 'occluding' the K+-conducting pathway.

Original languageEnglish
Pages (from-to)241-251
Number of pages11
JournalJournal of Membrane Biology
Volume115
Issue number3
DOIs
Publication statusPublished - May 1990
Externally publishedYes

Fingerprint

Calcium-Activated Potassium Channels
Aminoglycosides
Membranes
Brain
Binding Sites
Ribostamycin
Cations
Dibekacin
Gallamine Triethiodide
Anti-Bacterial Agents
Kanamycin
Neomycin
Lipid Bilayers
Constriction
Mouth
Ions
Pharmaceutical Preparations

Keywords

  • alkylamine
  • aminoglycoside antibiotics
  • Ca-activated K channel
  • channel blockade
  • synaptosomal membrane

ASJC Scopus subject areas

  • Physiology
  • Cell Biology
  • Biophysics

Cite this

Aminoglycoside blockade of Ca2+-activated K+ channel from rat brain synaptosomal membranes incorporated into planar bilayers. / Nomura, Kazushi; Naruse, Keiji; Watanabe, Kazuyoshi; Sokabe, Masahiro.

In: Journal of Membrane Biology, Vol. 115, No. 3, 05.1990, p. 241-251.

Research output: Contribution to journalArticle

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