Journal article
Nucleotide-gated KATP channels integrated with creatine and adenylate kinases: Amplification, tuning and sensing of energetic signals in the compartmentalized cellular environment
Molecular and cellular biochemistry, Vol.256(1), pp.243-256
01/2004
DOI: 10.1023/B:MCBI.0000009872.35940.7d
PMCID: PMC2760266
PMID: 14977185
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.
Details
- Title: Subtitle
- Nucleotide-gated KATP channels integrated with creatine and adenylate kinases: Amplification, tuning and sensing of energetic signals in the compartmentalized cellular environment
- Creators
- Vitaliy Selivanov - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Guggenheim 7 Rochester MN 55905 USAAlexey Alekseev - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Guggenheim 7 Rochester MN 55905 USADenice Hodgson - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Guggenheim 7 Rochester MN 55905 USAPetras Dzeja - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Guggenheim 7 Rochester MN 55905 USAAndre Terzic - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Guggenheim 7 Rochester MN 55905 USA
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biochemistry, Vol.256(1), pp.243-256
- DOI
- 10.1023/B:MCBI.0000009872.35940.7d
- PMID
- 14977185
- PMCID
- PMC2760266
- NLM abbreviation
- Mol Cell Biochem
- ISSN
- 0300-8177
- eISSN
- 1573-4919
- Publisher
- Kluwer Academic Publishers
- Language
- English
- Date published
- 01/2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094496502771
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