Ex Phys Chapter 13

Calciuneurin Calciuneurin is a phosphatase

Calciuneurin Calciuneurin is a phosphatase (i.e., enzyme that removes a phosphate group from molecules) activated by increases in cytosolic calcium and participates in several adaptive responses in muscle, including fiber growth/regeneration and the fast-to-slow fiber type transition that occurs as a result of endurance exercise training.

Ch 13

Endurance training programs that increase V̇O2 max commonly involve continuous dynamic exercise using a large muscle mass (e.g., running, cycling, or swimming)for 20 to 60 minutes per session, three or more times per week at an intensity >50% V̇O2 max

Ch 13

if a muscle is engaged in endurance exercise training, the primary adaptations are increases in capillaries and mitochondria volume, which increase the capacity of the muscle to produce energy aerobically. If a muscle is engaged in heavy resistance training, the primary adaptation is an increase in the quantity of the contractile proteins

Calmodulin-Dependent Kinase

Calmodulin-Dependent Kinase Calmodulin-dependent kinase (CaMK) is activated during endurance exercise training (16). This vital kinase exerts influence on exercise-induced muscle adaptation by contributing to the activation of PGC-1α. The primary upstream signal to activate CaMK is increased cytosolic calcium levels.

Calcium

For example, prolonged endurance exercise likely results in long periods of elevated calcium levels in the muscle cytosol, whereas resistance exercise would generate only short cycles of high cytosolic calcium levels

P38

Mitogen activated kinase p38 (p38) is an important signaling molecule that is activated in muscle fibers during endurance exercise. Although several cellular stresses can activate p38, it seems likely that exercise-induced production of free radicals is a major signal to activate p38 in muscle fibers. Once activated, p38 can contribute to mitochondrial biogenesis by activating PGC-1α.

NFκB

NFκB As mentioned previously, NFκB is a transcriptional activator that can be activated by free radicals that are produced in contracting muscles. Active NFκB promotes the expression of several antioxidant enzymes that protect muscle fibers against free radical-mediated injury.

Fick

training-induced changes in V̇O2 max occur due to increased maximal cardiac output, increased maximal a-v̅O2 difference, or some combination of both.V̇O2 max = Maximal cardiac output × (maximal a-v̅O2 difference)

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individuals with a low V̇O2 max prior to training can experience improvements with relatively low training intensities (e.g., 40% to 50% V̇O2 max), whereas individuals with high V̇O2 max values may require higher training intensities (e.g., >70% V̇O2 max)

ENDURANCE TRAINING: EFFECTS ON PERFORMANCE AND HOMEOSTASIS

Endurance training results in a more rapid transition from rest to steady-state exercise

Summary

IN SUMMARY Muscle adaptations that occur in response to sprint training vary depending upon the duration of exercise. Short-duration (10 to 30 seconds) sprint exercise training results in increased muscle buffer capacity, increases in the size of fast (type II) muscle fibers, and an improved ability to generate ATP via anaerobic energy systems. High-intensity exercise training involving intervals of 30 seconds or more promotes adaptations in both anaerobic and aerobic energy systems (i.e., increased mitochondrial biogenesis).

summary

Resistance training increases the synthesis of contractile proteins in muscle; this results in an increase in the cross-sectional area of the fiber. Resistance training-induced increases in protein synthesis occur via an increase in translation, which is controlled by the mTOR signaling pathway. Resistance exercise increases muscle levels of phosphatidic acid and Rheb. Both of these molecules are capable of activating mTOR signaling, which subsequently increases muscle protein synthesis. Resistance training results in parallel increases in muscle fiber cross-sectional area and increased numbers of myonuclei. Satellite cells are the source of additional myonuclei in muscle fibers, and the addition of myonuclei to muscle fibers is a requirement to achieve maximal fiber hypertrophy in response to resistance training.

Secondary Messengers in Skeletal Muscle

AMPK AMPK is an important signaling molecule that is activated during both high-intensity interval training, and submaximal endurance exercise training due to changes in muscle fiber phosphate/energy levels. This key molecule regulates numerous energy-producing pathways in muscle by stimulating glucose uptake and fatty acid oxidation during exercise. AMPK is also linked to the control of muscle gene expression by activating transcription factors associated with fatty acid oxidation and mitochondrial biogenesis. Interestingly, AMPK can inhibit components of the mTOR signaling pathway; the importance of this fact will be discussed later.

Summary

After stoppage of exercise training, V̇O2 max begins to decline quickly and can decrease by ~8% within 12 days after cessation of training, and declines by almost 20% following 84 days of detraining. The decrease in V̇O2 max with cessation of training is due to a decrease in both maximal stroke volume and oxygen extraction, the reverse of what happens with training. Exercise performance during submaximal exercise tasks also declines rapidly in response to detraining, due primarily to a decrease in the number of mitochondria in muscle fibers.

Summary

Endurance training programs that increase V̇O2 max involve a large muscle mass in continuous activity for 20 to 60 minutes per session, three or more times per week, at an intensity of 50% to 85% V̇O2 max. Similiar to continuous endurance training, high-intensity interval training also improves V̇O2 max. Although V̇O2 max increases an average of about 15% to 20% as a result of an endurance training program, the largest training-induced increases in V̇O2 max generally occur in those genetically gifted individuals who are often referred to as "high responders" to endurance training adaptations. Genetic predisposition accounts for about 50% of one's V̇O2 max value. Very strenuous and/or prolonged endurance training can increase V̇O2 max in normal sedentary individuals by up to 50%.

summary

In healthy, sedentary subjects, the training-induced improvements in V̇O2 max that occur following short-term training (i.e., ~4 months) are due to increases in maximal cardiac output alone. However, the training-induced improvements in V̇O2 max that occur following long duration training (i.e., 32 months) are the result of both increases in maximal cardiac output (i.e., stroke volume increases) and an increase in the a-v̅O2 difference. The training-induced increase in maximal stroke volume is due to both an increase in preload and a decrease in afterload. The increased preload is primarily due to an increase in end diastolic ventricular volume and the associated increase in plasma volume. The decreased afterload is due to a decrease in the arteriolar constriction in the trained muscles, increasing maximal muscle blood flow with no change in the mean arterial blood pressure. The training-induced increase in the a-v̅O2 difference is due to an increase in the capillary density of the trained muscles, which is needed to accept the increase in maximal muscle blood flow. The greater capillary density allows for a slow red blood cell transit time through the muscle, providing enough time for oxygen diffusion from the capillary into the muscle fiber.

Mechanical Stimuli

In particular, the high levels of mechanical stretch that occur across the muscle membrane during resistance training is the primary signal that promotes contractile protein synthesis, resulting in muscle hypertrophy.

Summary

Increases in strength due to short-term (8 to 20 weeks) resistance training are largely the result of changes in the nervous system, whereas gains in strength during long-term training programs are due to an increase in the size of the muscle. Whether or not hyperplasia occurs in response to resistance training remains controversial. Nonetheless, current evidence suggests that most (90% to 95%) of the increase in muscle size following resistance training occurs due to an increase in muscle hypertrophy and not hyperplasia. Prolonged periods of resistance training can promote a fast-to-slow shift in muscle fiber types. Most of this training-induced fiber shift is the conversion of type IIx to type IIa fibers, with no increase in the number of type I fibers. Whether resistance training improves muscle oxidative properties remains controversial. However, it is possible that long-term and high-volume resistance training programs can improve muscle oxidative capacity and increase capillary number around the trained fibers. Resistance training improves the antioxidant capacity of the trained muscle fibers.

Summary

Independent of the type of exercise stimulus (i.e., endurance or resistance exercise), the training-induced adaptation that occurs in muscle fibers is the result of an increase in the amount of specific proteins. The exercise-induced adaptations in skeletal muscle fibers are specific to the type of exercise stimulus (i.e., resistance vs. endurance exercise). Exercise-induced muscle adaptation occurs due to the coordination between primary and secondary signaling pathways in muscle fibers. Four primary signals for exercise-induced muscle adaptation include muscle stretch, increases in cellular free calcium, elevated free radicals, and decreases in muscle phosphate/energy levels. These primary signals then activate downstream secondary signaling pathways to promote gene expression. Seven secondary signaling molecules that contribute to exercise-induced muscle adaptation include AMPK, p38, PGC-1α, CaMK, calcineurin, NFκB, and mTOR. These signaling molecules are activated via one of four primary signaling pathways and act directly or indirectly to increase gene expression of specific muscle proteins.

summary

Individuals who engage in concurrent resistance training and high-intensity endurance exercise training often report that concurrent training impairs strength gains. Several mechanisms can potentially explain why concurrent training may impair strength gains. These include neural factors, low muscle glycogen content, overtraining, and depressed protein synthesis. Concurrent resistance and endurance exercise bouts can theoretically impair protein synthesis following resistance exercise training. The science behind this prediction is illustrated in Figure 13.22

Summary

The biochemical changes in muscle due to endurance training influence the heart rate and ventilatory responses to exercise. The reduction in "feedback" from chemoreceptors in the trained muscle and a decreased need to recruit motor units to accomplish an exercise task result in reduced sympathetic nervous system, heart rate, and ventilation responses to submaximal exercise. Endurance exercise training also reduces central command outflow during submaximal exercise that results in a lower heart rate and ventilatory response during exercise.

Detraining following endurance training

The initial decrease (first 12 days) in V̇O2 max was due entirely to the decrease in stroke volume, because the heart rate and a-v̅O2 difference remained the same or increased. This sudden decrease in maximal stroke volume appears to be due to the rapid loss of plasma volume with detraining (18). When plasma volume was artificially restored by infusion, V̇O2 max increased toward pre-detraining values (18). This was confirmed in a study in which a 200 to 300 ml expansion of plasma volume was shown to increase V̇O2 max, even though the hemoglobin concentration was reduced (19).

summary

The stoppage of resistance training results in a loss of muscular strength and muscle atrophy. However, compared to the rate of detraining following endurance exercise, the rate of detraining from resistance exercise is slower. Rapid muscular adaptations occur as a result of strength training in previously trained individuals. Maximal dynamic strength can be maintained for up to 12 weeks with reduced training frequency.

PGC-1α

This key molecule is activated by both high-intensity interval training and submaximal endurance exercise and is considered the master regulator of mitochondrial biogenesis in cells (72). Indeed, PGC-1α assists transcriptional activators that promote mitochondrial biogenesis in skeletal muscle following endurance training. Furthermore, PGC-1α regulates many other endurance exercise-mediated changes in skeletal muscle, including the formation of new capillaries (angiogenesis), a fast-to-slow muscle fiber type shift, and synthesis of antioxidant enzymes (72). PGC-1α also plays a role in exercise-induced increases in muscle's ability to metabolize fat and to take up glucose into the muscle fiber. Several factors activate PGC-1α during exercise, including AMPK and p38.

summary

Three primary signals involved in endurance exercise-induced muscle adaptation are increases in cellular free calcium, elevated free radicals, and decreases in muscle phosphate/energy levels. These primary signals then activate one or more of the downstream secondary signaling pathways to promote gene expression. Six secondary signaling molecules that contribute to endurance exercise-induced muscle adaptation include AMPK, PGC-1α, calcineurin, CaMK, p38, and NFκB. Both active calcineurin and PGC-1α play important roles in endurance exercise-induced fast-to-slow fiber transformations. Collectively, active CaMK, AMPK, and p38 all participate in activation of PGC-1α. Active PGC-1α is the master regulator for mitochondrial biogenesis. Both active PGC-1α and NFκB contribute to the exercise-induced increase in muscle antioxidants.

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abundant evidence also reveals that high-intensity interval training (i.e., 30 seconds all-out efforts) also improves V̇O2 max

Detraining following endurance training

ecrease in V̇O2 max is due to the decrease in the a-v̅O2 difference.This was associated with a decrease in muscle mitochondria, whereas capillary density remained unchanged. The overall oxidative capacity of skeletal muscle was reduced, with the percentage of type IIa fibers decreasing from 43% to 26% and the percentage of type IIx fibers increasing from 5% to 19% (20, 21). This detraining-induced slow-to-fast fiber type shift is opposite to the fast-to-slow shift in muscle fiber type that occurs during endurance exercise training. Detraining not only decreases V̇O2 max, inactivity can also impair submaximal endurance performance. For example, as few as 14 days of disrupted training (e.g., detraining) can significantly impair submaximal exercise performance (e.g., performance in 10K run). This is due primarily to a decrease in muscle mitochondria (63, 105). Indeed, muscle mitochondrial oxidative capacity undergoes rapid changes at both the onset and termination of exercise training. Figure 13.15

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endurance training programs of two- to three-months duration typically cause an increase in V̇O2 max between 15% and 20%, the range of improvement can be as low as 2% to 3% for those who start the program with high V̇O2 max values (23), and as high as 50% for individuals with low initial V̇O2 max values or the genetic potential for large improvements in V̇O2 max with training

What causes the maximal stroke volume and the maximal arteriovenous oxygen difference to increase as a result of endurance training? The answers are provided in the next two sections.

stroke volume is the amount of blood ejected from the heart with each beat and is equal to the difference between end diastolic volume (EDV) and end systolic volume (ESV).

Phosphate/Muscle Energy Levels

the most important in exercise-induced muscle adaptation is activation of a secondary messenger called 5'adenosine monophosphate activated protein kinase (AMPK). Indeed, AMPK is an important downstream signaling molecule that senses the energy state of the muscle and is activated by both high-intensity interval training and prolonged endurance exercise. This important kinase regulates numerous muscle signaling processes leading to muscle adaptation in response to endurance training