Oxygen regulation and limitation to cellular respiration in mouse skeletal muscle in vivo

Denen Studien sier noe ekstremt viktig: Oksygen, mye eller lite, har ingen ting med regulering av cellerespirasjon å gjøre annet enn å være tilgjengelig som et substrat (altså noe cellene kan leve på). De nevner at oksygen bare blir et problem om det går under 2-3 mmHg. Og at blodceller virker som enn buffer ved at de slipper av oxygen for å holde det ovenfor

Marcinek et.al. 2003. Oxygen regulation and limitation to cellular respiration in mouse skeletal muscle in vivo.

http://ajpheart.physiology.org/content/285/5/H1900.full

Therefore, we reject a regulatory role for oxygen in cellular respiration and conclude that oxygen acts as a simple substrate for respiration under physiological conditions.

LOW OXYGEN TENSIONS are characteristic of active muscle. During maximal aerobic exercise, intracellular PO2 in skeletal muscle falls to as low as 2–3 mmHg based on an average myoglobin (Mb) saturation of ∼50% (2427). The intracellular oxygen tension at the maximal rate of sustained exercise sets the lower end of the range of physiologically relevant intracellular PO2 values. These values are just above the threshold where isolated mitochondria (12,29), isolated cells (3940), and intact muscle (28) begin to become oxygen limited. Thus the intracellular PO2 reached during heavy muscle exercise may approach the threshold for limiting cellular respiration in vivo.

Experiments in isolated mitochondria and cells have shown that the respiration rate remains relatively constant over the physiological PO2 range (1236), with a clear reduction occurring only at PO2 below 2–3 mmHg.

Our in vivo results from the mouse hindlimb indicate that until a threshold PO2 is reached (2–3 mmHg), there is no effect of oxygen tension on the phosphorylation state of the cell.

In mouse skeletal muscle in vivo, oxygen tension in the physiological range had no significant effect on cellular respiration over a threefold range of baseline rates of oxygen consumption. This is the expected outcome if oxygen is acting as a simple substrate with no significant regulatory role under physiological conditions.

Thus we found no evidence for a change in the relationship between respiration rate and intracellular PO2 with a greater than threefold increase in the fully oxygenated respiration rate. This leads us to conclude that oxygen is not limiting to cellular oxygen consumption and, therefore, does not play a significant role in regulating cellular respiration in vivo under these conditions.

Studies on exercising human muscle support the conclusion that oxygen tension in skeletal muscle does not fall to levels low enough to significantly inhibit cellular respiration except under extreme physiological conditions [i.e., maximum oxygen consumption (V̇O2 max) in trained individuals]. These studies indicate that Mb saturations at the aerobic capacity of human skeletal muscle are ∼50% in vivo (2.4 mmHg) (2427). Our results indicate that above this intracellular PO2, there is little effect of oxygen tension on the cellular respiration rate over the range tested in the present study.

Decreasing the capacity for oxygen delivery by breathing hypoxic air was found to drop Mb saturation below the 50% level and to reduce oxygen consumption during exercise (26). In contrast, supplementing oxygen by breathing of hyperoxic air during a maximum oxygen consumption test either did not effect or resulted in a small increase (∼10%) in V̇O2 max (625).

The transition between oxygen-independent and oxygen-dependent respiration in vivo also occurs in this range of intracellular oxygen tensions (2–3 mmHg). Therefore, an important role of Mb in skeletal muscle may be as an oxygen buffer to help maintain intracellular PO2 above the point at which it becomes limiting to cellular respiration.

In conclusion, the findings of the present study lead us to reject the hypothesis that oxygen plays a regulatory role in cellular respiration over the physiological range of intracellular oxygen tensions. This conclusion is based on the absence of interaction between [PCr], pH (and therefore phosphorylation state), oxygen consumption, and PO2 above 3 mmHg over a greater than threefold range in oxygen consumption rates. These results are consistent with the hypothesis that oxygen acts as a simple substrate for cellular respiration over the physiological range of oxygen tensions.

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