RESEARCH – January 2008

Importance of cellular organization in regulation of respiration in cardiac muscle cells

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Abstract

The AIM OF THIS WORK was to compare the cellular regulation of mitochondrial respiration in permeabilized cardiomyocytes, where intermyofibrillar mitochondria are arranged in a highly ordered crystal-like pattern, and in the HL-1 cells from mouse heart.
METHODS. Two types of HL-1 cells were used: 1) HL-1 beating cells (B HL-1 cells) which contain quite organized sarcomeres and represent somewhat of a hybrid between an embryonic myocyte and an adult myocyte and 2) HL-1 non-beating cells (NB HL-1 cells) without sarcomeres.
RESULTS. Striking differences were observed in the kinetics of respiration regulation by exogenous ADP between these cells: apparent Km for exogenous  ADP was by an order of magnitude lower in permeabilized non-beating NB HL-1 cells without sarcomeres (25 ± 4 μM) than in permeabilized primary cardiomyocytes (486 ± 51 μM), and intermediate in normally cultured HL-1 cells (110 ± 18 μM). High affinity for exogenous ADP in NB HL-1 cells demonstrates the absence of significant diffusion restrictions in these cells in contrast to adult cardiomyocytes.
CONCLUSION. The results of this study show that in normal adult cardiomyocytes intracellular local restrictions of diffusion of adenine nucleotides and metabolic feedback regulation of respiration via phosphotransfer networks are related to the complex structural organization of these cells.