Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 52, Issue 2, Pages 401-409Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2011.06.007
Keywords
ADP; ATP; ATP-sensitive K+ channel; Energy metabolism; Ion homeostasis; Macromolecular complex; Partitioning; Phosphotransfer; Submembrane
Categories
Funding
- NHLBI NIH HHS [R01 HL085744, R01 HL085744-04, R01 HL085744-05] Funding Source: Medline
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Orchestrated excitation-contraction coupling in heart muscle requires adequate spatial arrangement of systems responsible for ion movement and metabolite turnover. Co-localization of regulatory and transporting proteins into macromolecular complexes within an environment of microanatomical cell components raises intracellular diffusion barriers that hamper the mobility of metabolites and signaling molecules. Compared to substrate diffusion in the cytosol, diffusional restrictions underneath the sarcolemma are much larger and could impede ion and nucleotide movement by a factor of 10(3)-10(5). Diffusion barriers thus seclude metabolites within the submembrane space enabling rapid and vectorial effector targeting, yet hinder energy supply from the bulk cytosolic space implicating the necessity for a shunting transfer mechanism. Here, we address principles of membrane protein compartmentation, phosphotransfer enzyme-facilitated interdomain energy transfer, and nucleotide signal dynamics at the subsarcolemma-cytosol interface. This article is part of a Special Issue entitled Local Signaling in Myocytes. (C) 2011 Elsevier Ltd. All rights reserved.
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