Killing K channels with TEA+

Kamran Khodakhah, Alexey Melishchuk, Clay M. Armstrong

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Tetraethylammonium (TEA+) is widely used for reversible blockade of K channels in many preparations. We noticed that intracellular perfusion of voltage-clamped squid giant axons with a solution containing K+ and TEA+ irreversibly decreased the potassium current when there was no K+ outside. Five minutes of perfusion with 20 mM TEA+, followed by removal of TEA+, reduced potassium current to <5% of its initial value. The irreversible disappearance of K channels with TEA+ could be prevented by addition of ≤ 10 mM K+ to the extracellular solution. The rate of disappearance of K channels followed first-order kinetics and was slowed by reducing the concentration of TEA+. Killing is much less evident when an axon is held at -110 mV to tightly close all of the channels. The longer-chain TEA+ derivative decyltriethylammonium (C10+) had irreversible effects similar to TEA+. External K+ also protected K channels against the irreversible action of C10+. It has been reported that removal of all K+ internally and externally (dekalification) can result in the disappearance of K channels, suggesting that binding of K+ within the pore is required to maintain function. Our evidence further suggests that the crucial location for K+ binding is external to the (internal) TEA+ site and that TEA+ prevents refilling of this location by intracellular K+. Thus in the absence of extracellular K+, application of TEA+ (or C10+) has effects resembling dekalification and kills the K channels.

Original languageEnglish (US)
Pages (from-to)13335-13338
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number24
DOIs
StatePublished - Nov 25 1997
Externally publishedYes

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Axons
Potassium
Perfusion
Decapodiformes
Tetraethylammonium
N,N,N-triethyl-1-dodecylammonium

Keywords

  • Channel block
  • Decyltriethylammonium
  • Dekalification
  • Tetraethylammonium

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Killing K channels with TEA+ . / Khodakhah, Kamran; Melishchuk, Alexey; Armstrong, Clay M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 24, 25.11.1997, p. 13335-13338.

Research output: Contribution to journalArticle

Khodakhah, Kamran ; Melishchuk, Alexey ; Armstrong, Clay M. / Killing K channels with TEA+ In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 24. pp. 13335-13338.
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AB - Tetraethylammonium (TEA+) is widely used for reversible blockade of K channels in many preparations. We noticed that intracellular perfusion of voltage-clamped squid giant axons with a solution containing K+ and TEA+ irreversibly decreased the potassium current when there was no K+ outside. Five minutes of perfusion with 20 mM TEA+, followed by removal of TEA+, reduced potassium current to <5% of its initial value. The irreversible disappearance of K channels with TEA+ could be prevented by addition of ≤ 10 mM K+ to the extracellular solution. The rate of disappearance of K channels followed first-order kinetics and was slowed by reducing the concentration of TEA+. Killing is much less evident when an axon is held at -110 mV to tightly close all of the channels. The longer-chain TEA+ derivative decyltriethylammonium (C10+) had irreversible effects similar to TEA+. External K+ also protected K channels against the irreversible action of C10+. It has been reported that removal of all K+ internally and externally (dekalification) can result in the disappearance of K channels, suggesting that binding of K+ within the pore is required to maintain function. Our evidence further suggests that the crucial location for K+ binding is external to the (internal) TEA+ site and that TEA+ prevents refilling of this location by intracellular K+. Thus in the absence of extracellular K+, application of TEA+ (or C10+) has effects resembling dekalification and kills the K channels.

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