Journal article
Signaling in Channel/Enzyme Multimers: ATPase Transitions in SUR Module Gate ATP-Sensitive K + Conductance
Neuron (Cambridge, Mass.), Vol.31(2), pp.233-245
2001
DOI: 10.1016/S0896-6273(01)00356-7
PMID: 11502255
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.
Details
- Title: Subtitle
- Signaling in Channel/Enzyme Multimers: ATPase Transitions in SUR Module Gate ATP-Sensitive K + Conductance
- Creators
- Leonid V ZingmanAlexey E AlekseevMartin BienengraeberDenice HodgsonAmy B KargerPetras P DzejaAndre Terzic
- Resource Type
- Journal article
- Publication Details
- Neuron (Cambridge, Mass.), Vol.31(2), pp.233-245
- Publisher
- Elsevier Inc
- DOI
- 10.1016/S0896-6273(01)00356-7
- PMID
- 11502255
- ISSN
- 0896-6273
- eISSN
- 1097-4199
- Language
- English
- Date published
- 2001
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094342202771
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