Mitochondrial respiratory control can compensate for intracellular O(2) gradients in cardiomyocytes at low PO(2).
In isolated single cardiomyocytes with moderately elevated mitochondrial respiration, direct evidence for intracellular radial gradients of oxygen concentration was obtained by subcellular spectrophotometry of myoglobin (Mb). When oxygen consumption was increased by carbonyl cyanide m-chlorophenylhydrazone (CCCP) during superfusion of cells with 4% oxygen, PO(2) at the cell core dropped to 2.3 mmHg, whereas Mb near the plasma membrane was almost fully saturated with oxygen. Subcellular NADH fluorometry demonstrated corresponding intracellular heterogeneities of NADH, indicating suppression of mitochondrial oxidative metabolism due to relatively slow intracellular oxygen diffusion. When oxygen consumption was increased by electrical pacing in 2% oxygen, radial oxygen gradients of similar magnitude were demonstrated (cell core PO(2) = 2.6 mmHg). However, an increase in NADH fluorescence at the cell core was not detected. Because CCCP abolished mitochondrial respiratory control while it was intact in electrically paced cardiomyocytes, we conclude that mitochondria with intact respiratory control can sustain electron transfer with reduced oxygen supply. Thus mitochondrial intrinsic regulation can compensate for relatively slow oxygen diffusion within cardiomyocytes.
Takahashi
Eiji
E
Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. eiji@med.id.yamagata-u.ac.jp
Asano
Koji
K
D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014475:Uncoupling Agents / Q000494:pharmacology
D009211:Myoglobin; D014475:Uncoupling Agents; D009243:NAD; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D010100:Oxygen