Difference between revisions of "Dynamics of activation"

Revision as of 22:23, 30 March 2021

For model validation, dynamics of activation, ATP, PCr, glycolysis, oxidative phosphorylation. Ver. 1.0.

The rate of muscles ATP hydrolysis

The rate of muscles ATP hydrolysis with a stepwise increase in external load increases almost immediately (as seen by the rate of ADP formation) (Broxterman et al., 2017 [1]; Bartlett et al., 2020 [2]):

Figure from (Bartlett et al., 2020) [2], Changes in muscle ADP across time during trials.

Figure from (Broxterman et al., 2017) [1], Changes in muscle ADP across time.

The rate of muscles PCr hydrolysis

The rate of muscles PCr hydrolysis with a stepwise increase in external load increases almost immediately (Layec et al., 2008 [3]; Cannon et al., 2014 [4]; Fiedler et al., 2016 [5]; Broxterman et al., 2017 [1]; Bartlett et al., 2020 [2]).

Changes in muscle PCr across time

Figure from (Layec et al., 2008) [3], Changes in muscle PCr across time

Figure from (Bartlett et al., 2020) [2], Changes in muscle PCr across time during trials

In tests with a stepwise increase in external load, the following dynamics of changes in the PCr concentration is observed (Schocke et al., 2005 [6]; Greiner et al., 2007 [7]).

Figure from (Greiner et al., 2007) [7], changes in the PCr concentration across time

Figure from (Schocke et al., 2005) [6], changes in the PCr concentration across time According to those data, with a frequent stepwise increase or with a gradual increase in external load, the rate of PCr hydrolysis should be constant.

The rate of muscles glycolysis in general

Figure from (Larsen et al., 2014) [8], Rates of ATP synthesis during a 24-s maximal voluntary knee extension contraction (MVC), ATP provision from glycolysis (B, ATPGLY).

Calculation of glycolytic ATP synthesis from (Larsen et al., 2014) [8]:

Figure from (Layec et al., 2015) [9], The rate of ATP synthesis through anaerobic glycolysis (A), oxidative phosphorylation (B)

Figure from (Walter et al., 1999) [10], Glycogenolytic and glycolytic rates in the medial gastrocnemius during maximal rate exercise.

Calculation of glycolytic ATP synthesis from (Walter et al., 1999) [10]:

Dynamics of the activity of some glycolytic enzymes

Calcium-regulated PFK-1 activity increases almost instantly (Schmitz et al., 2013) [11].

Figure from (Schmitz et al., 2013) [11], PFK-1 (de)activation kinetics

The PFK-1 activity is regulated by metabolites also

Figure from (Schmitz et al., 2013) [11], Schematic representation of the regulation of PFK-1 as modeled in each model configuration. Model configuration (B) represented the hypothesis in which binding of calcium-calmodulin complexes to PFK-1 partly reliefs ATP inhibition of the enzyme independent of the levels of ADP and AMP. Model configuration (C) represented the hypothesis in which binding of calcium-calmodulin complexes partly reliefs ATP inhibition by enhancing the competitive binding of AMP and ADP to the inhibitory ATP site.

Glycogen phosphorylase and PDH activity increases within seconds (Parolin et al., 1999) [12].

Figure from (Parolin et al., 1999) [12], Regulation of skeletal muscle glycogen phosphorylase and PDH during maximal intermittent exercise.

Dynamics of oxidative phosphorylation activity at the onset of exercise

Despite the sufficient amount of oxygen bound to myoglobin in the muscles, oxidative phosphorylation begins with some delay with a stepwise increase in load (Grassi et al., 2005 [13]; Richardson et al., 2015 [14]) with a time lag of about 10 seconds.

Figure from (Grassi et al., 2005) [13], Time courses of changes of deoxygenated Hb + Mb concentration, as well as of oxygenated Hb + Mb concentration.

Figure from (Richardson et al., 2015) [14], Tracing of the deoxygenated myoglobin (deoxy-Mb) signal at the onset of moderate-intensity exercise.

During repeated exercise, the oxygen-uptake rate increases faster compared to the first bout of exercise. This must be taken into account when modelling intermittent loads.

Figure from (Bangsbo et al., 2001) [15], Thigh oxygen uptake during EX1 and EX2.

Figure from (Combes et al., 2016) [16], VO2 fluctuations for each exercise transition

Data for model validation, [H+]

Table from (Hargreaves et al., 1998) [17].

Table from (Hargreaves et al., 1998) [17].

Figure and table from (Spriet et al., 1989) [18], maximal cycling for 30 s, each separated by 4 min of rest

Figure from (Davies et al., 2017) [19], PCr and pH responses to intermittent or continuous exercise.

Figure from (Chidnok et al., 2013) [20], Muscle [PCr] and pH responses during high-intensity intermittent exercise.

Overall, MRS studies show pH recovery is too fast compared to studies that used biochemical pH measurements, see below.

Figures from (Sahlin et al., 1976) [21],

Table from (Parolin et al., 1999) [12].

Figure from (Parolin et al., 1999) [12].

Figures from (Kushmerick et al., 1992) [12], Data from cat muscles, The time courses of changes in intracellular pH during stimulation at the various rates for the biceps and for the soleus.

References

1. Broxterman RM, Layec G, Hureau TJ, Morgan DE, Bledsoe AD, Jessop JE, Amann M, and Richardson RS. Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle Afferents. Med Sci Sports Exerc. 2017 Dec;49(12):2404-2413. DOI:10.1249/MSS.0000000000001391 | PubMed ID:28767527 | HubMed [1]
2. Bartlett MF, Fitzgerald LF, Nagarajan R, Hiroi Y, and Kent JA. Oxidative ATP synthesis in human quadriceps declines during 4 minutes of maximal contractions. J Physiol. 2020 May;598(10):1847-1863. DOI:10.1113/JP279339 | PubMed ID:32045011 | HubMed [2]
3. Error fetching PMID 18483819: [3]
4. Error fetching PMID 25281731: [4]
5. Error fetching PMID 27562396: [5]
6. Error fetching PMID 15517340: [6]
7. Error fetching PMID 17206438: [7]
8. Error fetching PMID 24612773: [8]
9. Error fetching PMID 26041112: [9]
10. Error fetching PMID 10457099: [10]
11. Error fetching PMID 23114964: [11]
12. Parolin ML, Chesley A, Matsos MP, Spriet LL, Jones NL, and Heigenhauser GJ. Regulation of skeletal muscle glycogen phosphorylase and PDH during maximal intermittent exercise. Am J Physiol. 1999 Nov;277(5):E890-900. DOI:10.1152/ajpendo.1999.277.5.E890 | PubMed ID:10567017 | HubMed [12]
13. Error fetching PMID 16177610: [13]
14. Error fetching PMID 25830362: [14]
15. Error fetching PMID 11350777: [15]
16. Error fetching PMID 26943697: [16]
17. Error fetching PMID 9572818: [17]
18. Error fetching PMID 2917960: [18]
19. Error fetching PMID 28776675: [19]
20. Error fetching PMID 24068048: [20]
21. Error fetching PMID 13343: [21]
22. Error fetching PMID 1415510: [22]