Phosphotransfer reactions in the regulation of ATP-sensitive K+ channels

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

ATP-sensitive K+ (K(ATP)) channels are nucleotide-gated channels that couple the metabolic status of a cell with membrane excitability and regulate a number of cellular functions, including hormone secretion and cardioprotection. Although intracellular ATP is the endogenous inhibitor of K(ATP) channels and ADP serves as the channel activator, it is still a matter of debate whether changes in the intracellular concentrations of ATP, ADP, and/or in the ATP/ADP ratio could account for the transition from the ATP- liganded to the ADP-liganded channel state. Here, we overview evidence for the role of cellular phosphotransfer cascades in the regulation of K(ATP) channels. The microenvironment of the K(ATP) channel harbors several phosphotransfer enzymes, including adenylate, creatine, and pyruvate kinases, as well as other glycolytic enzymes that are able to transfer phosphoryls between ATP and ADP in the absence of major changes in cytosolic levels of adenine nucleotides. These phosphotransfer reactions are governed by the metabolic status of a cell, and their phosphotransfer rate closely correlates with K(ATP) channel activity. Adenylate kinase catalysis accelerates the transition from ATP to ADP, leading to K(ATP) channel opening, while phosphotransfers driven by creatine and pyruvate kinases promote ADP to ATP transition and channel closure. Thus, through delivery and removal of adenine nucleotides at the channel site, phosphotransfer reactions could regulate ATP/ADP balance in the immediate vicinity of the channel and thereby the probability of K(ATP) channel opening. In this way, phosphotransfer reactions could provide a transduction mechanism coupling cellular metabolic signals with K(ATP) channel-associated functions.

Original languageEnglish (US)
Pages (from-to)523-529
Number of pages7
JournalFASEB Journal
Volume12
Issue number7
StatePublished - 1998

Fingerprint

adenylate kinase
pyruvate kinase
potassium channels
creatine kinase
Adenosine Triphosphate
hormone secretion
enzymes
catalytic activity
Adenosine Diphosphate
nucleotides
cells
Adenylate Kinase
adenine nucleotides
Pyruvate Kinase
Adenine Nucleotides
Creatine Kinase

Keywords

  • Adenylate kinase
  • Creatine kinase
  • Glycolysis
  • K(ATP) channel
  • Metabolic signaling
  • Pyruvate kinase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Phosphotransfer reactions in the regulation of ATP-sensitive K+ channels. / Dzeja, Petras P; Terzic, Andre.

In: FASEB Journal, Vol. 12, No. 7, 1998, p. 523-529.

Research output: Contribution to journalArticle

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