Signaling in channel/enzyme multimers: ATPase transitions in SUR module gate ATP-sensitive K + conductance

Leonid V. Zingman, Alexey E. Alekseev, Martin Bienengraeber, Denice Hodgson, Amy B. Karger, Petras P Dzeja, Andre Terzic

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

ATP-sensitive potassium (K ATP) channels are bifunctional multimers assembled by an ion conductor and a sulfonylurea receptor (SUR) ATPase. Sensitive to ATP/ADP, K ATP channels are vital metabolic sensors. However, channel regulation by competitive ATP/ADP binding would require oscillations in intracellular nucleotides incompatible with cell survival. We found that channel behavior is determined by the ATPase-driven engagement of SUR into discrete conformations. Capture of the SUR catalytic cycle in prehydrolytic states facilitated pore closure, while recruitment of posthydrolytic intermediates translated in pore opening. In the cell, channel openers stabilized posthydrolytic states promoting K ATP channel activation. Nucleotide exchange between intrinsic ATPase and ATP/ADP-scavenging systems defined the lifetimes of specific SUR conformations gating K ATP channels. Signal transduction through the catalytic module provides a paradigm for channel/enzyme operation and integrates membrane excitability with metabolic cascades.

Original languageEnglish (US)
Pages (from-to)233-245
Number of pages13
JournalNeuron
Volume31
Issue number2
DOIs
StatePublished - Aug 2 2001

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Sulfonylurea Receptors
Adenosine Triphosphatases
Adenosine Triphosphate
Enzymes
Adenosine Diphosphate
Nucleotides
KATP Channels
Signal Transduction
Cell Survival
Ions
Membranes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Signaling in channel/enzyme multimers : ATPase transitions in SUR module gate ATP-sensitive K + conductance. / Zingman, Leonid V.; Alekseev, Alexey E.; Bienengraeber, Martin; Hodgson, Denice; Karger, Amy B.; Dzeja, Petras P; Terzic, Andre.

In: Neuron, Vol. 31, No. 2, 02.08.2001, p. 233-245.

Research output: Contribution to journalArticle

Zingman, Leonid V. ; Alekseev, Alexey E. ; Bienengraeber, Martin ; Hodgson, Denice ; Karger, Amy B. ; Dzeja, Petras P ; Terzic, Andre. / Signaling in channel/enzyme multimers : ATPase transitions in SUR module gate ATP-sensitive K + conductance. In: Neuron. 2001 ; Vol. 31, No. 2. pp. 233-245.
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