Binding of a gating modifier toxin induces intersubunit cooperativity early in the Shaker K channel's activation pathway

Jon T Sack, Richard W. Aldrich

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Potassium currents from voltage-gated Shaker K channels activate with a sigmoid rise. The degree of sigmoidicity in channel opening kinetics confirms that each subunit of the homotetrameric Shaker channel undergoes more than one conformational change before the channel opens. We have examined effects of two externally applied gating modifiers that reduce the sigmoidicity of channel opening. A toxin from gastropod mucus, 6-bromo-2-mercaptotryptamine (BrMT), and divalent zinc are both found to slow the same conformational changes early in Shaker's activation pathway. Sigmoidicity measurements suggest that zinc slows a conformational change independently in each channel subunit. Analysis of activation in BrMT reveals cooperativity among subunits during these same early steps. A lack of competition with either agitoxin or tetraethylammonium indicates that BrMT binds channel subunits outside of the external pore region in an allosterically cooperative fashion. Simulations including negatively cooperative BrMT binding account for its ability to induce gating cooperativity during activation. We conclude that cooperativity among K channel subunits can be greatly altered by experimental conditions.

Original languageEnglish (US)
Pages (from-to)119-132
Number of pages14
JournalJournal of General Physiology
Volume128
Issue number1
DOIs
StatePublished - 2006
Externally publishedYes

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Zinc
Activation Analysis
Voltage-Gated Potassium Channels
Gastropoda
Tetraethylammonium
Sigmoid Colon
Mucus
Potassium

ASJC Scopus subject areas

  • Physiology

Cite this

Binding of a gating modifier toxin induces intersubunit cooperativity early in the Shaker K channel's activation pathway. / Sack, Jon T; Aldrich, Richard W.

In: Journal of General Physiology, Vol. 128, No. 1, 2006, p. 119-132.

Research output: Contribution to journalArticle

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