Nucleotide-gated KATP channels integrated with creatine and adenylate kinases

Amplification, tuning and sensing of energetic signals in the compartmentalized cellular environment

Vitaliy A. Selivanov, Alexey E. Alekseev, Denice M. Hodgson, Petras P Dzeja, Andre Terzic

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Transmission of energetic signals to membrane sensors, such as the ATP-sensitive K+ (KATP) channel, is vital for cellular adaptation to stress. Yet, cell compartmentation implies diffusional hindrances that hamper direct reception of cytosolic energetic signals. With high intracellular ATP levels, KATP channels may sense not bulk cytosolic, but rather local submembrane nucleotide concentrations set by membrane ATPases and phosphotransfer enzymes. Here, we analyzed the role of adenylate kinase and creatine kinase phosphotransfer reactions in energetic signal transmission over the strong diffusional barrier in the submembrane compartment, and translation of such signals into a nucleotide response detectable by KATP channels. Facilitated diffusion provided by creatine kinase and adenylate kinase phosphotransfer dissipated nucleotide gradients imposed by membrane ATPases, and shunted diffusional restrictions. Energetic signals, simulated as deviation of bulk ATP from its basal level, were amplified into an augmented nucleotide response in the submembrane space due to failure under stress of creatine kinase to facilitate nucleotide diffusion. Tuning of creatine kinase-dependent amplification of the nucleotide response was provided by adenylate kinase capable of adjusting the ATP/ADP ratio in the submembrane compartment securing adequate KATP channel response in accord with cellular metabolic demand. Thus, complementation between creatine kinase and adenylate kinase systems, here predicted by modeling and further supported experimentally, provides a mechanistic basis for metabolic sensor function governed by alterations in intracellular phosphotransfer fluxes.

Original languageEnglish (US)
Pages (from-to)243-256
Number of pages14
JournalMolecular and Cellular Biochemistry
Volume256-257
Issue number1-2
StatePublished - Jan 2004

Fingerprint

Adenylate Kinase
KATP Channels
Creatine Kinase
Amplification
Nucleotides
Tuning
Adenosine Triphosphate
Membranes
Cell Compartmentation
Adenosine Triphosphatases
Facilitated Diffusion
Sensors
Adenosine Diphosphate
Fluxes
Enzymes

Keywords

  • ATP-sensiitve K channel
  • Heart
  • Intracellular compartment
  • Metabolic sensor
  • Nucleotide diffusion

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Nucleotide-gated KATP channels integrated with creatine and adenylate kinases : Amplification, tuning and sensing of energetic signals in the compartmentalized cellular environment. / Selivanov, Vitaliy A.; Alekseev, Alexey E.; Hodgson, Denice M.; Dzeja, Petras P; Terzic, Andre.

In: Molecular and Cellular Biochemistry, Vol. 256-257, No. 1-2, 01.2004, p. 243-256.

Research output: Contribution to journalArticle

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