Muscle III: Fatigue, Metabolism, and Adaptation

CSA, Muscle Mass, Fiber area (can be applied to a single fiber or a whole muscle), fiber diameter

things that affect force production per unit of contracting muscle tissue 

possible factors in changes in specific force 

central activation, NM transmission, sarcolemma excitability, E-C coupling (Ca release and sensitivity), crossbridge formation, force transmission, fiber type changes, fatigue, changes in connective tissue 

fatigue

transient decrease in muscle performance, associated with activity as there is a decrease in max force generating capacity, inability to maintain submax force, or inability to continue an activity, and is task specific

muscle fatigue definition 1

starting with maximum effort of an isolated muscle or muscle group that is subject to a fixed time of exercise, fatigue sets in after a relative decrease in percentage of force production, this amount can vary based on what is specified by the study

muscle fatigue definition 2

muscle starts at submax, output is kept fixed, time to task failure is principle failure, and fatigue is binary, example: holding 50% of max effort is held, when max effort can no longer reach that 50% threshold fatigue has been reached

things that relate to fatigue

supply and demand

supply

substrate utilization to regenerate ATP, substrate availability, enzyme abundance/activity, perfusion/vascularity (delivers oxygen)

demand

myosin heavy chain/crossbridges, sarcoplasmic reticulum re-uptake via SERCA, Na+/K+ ATPase

different enzymatic and biochemical profiles

feature of fibers that allows for optimization of resting metabolism vs peak metabolism, related to capillary and myoglobin content (red/dark vs white/light)

characteristics of Type I/IIa fibers 

more mitochondria, more capillaries, more oxidative enzymes, more lipid droplets, variable glycogen 

variable- may find different levels just depending on where you look

level of glycogen in different fiber types

metabolically expensive and space constraints

reason why muscle does not have the capacity to support maximal demand at all times

resting metabolism features 

primarily is driven by oxidative phosphorylation, and is post-prandial (meaning responds to what we eat/our diet)

PCr (phosphocreatine) breakdown through Creatine Kinase

mechanism that is used to replenish ATP during initial transition from rest to activity before oxidative phosphorylation and glycolysis is really able to kick in or catch up

PCr

an energy “capacitor” or buffer, very high in skeletal muscle and some in heart and brain, but low in liver, kidney, testes

FFA (through Oxphos)

during long duration endurance exercises, low intensity exercises body typically uses this supply in higher demands

glucose/glycogen

during high intensity exercise, body switches from FFA use to this supply, utilizing glycolysis

VO2 max

amount of oxygen that your body can effectively metabolize/use

sarcoplasmic reticulum

feature more extensive in fast fibers IIx/b (more so than IIa, though IIa has significant, and more so than I)

mysoin ATPase rate of ATP consumption

differences in this rate is what distinguishes different fiber types, example: ATP consumption is IIx> IIa > I

glycogen depletion 

mechanism of fatigue, seems to be a limiting factor for endurance activity, “the bonk”

lactic acid

a more correlational that causative factor of fatigue, actually has a number of benefits, acidosis can lower force, but does so minimally as physiological temperatures, but there may be neural involvement in response that leads to central inhibition

peripheral fatigue 

fatigue that happens at the periphery, due to NMJ transmission, electrical fatigue, ADP/Pi buildup that inhibits cross bridge formation, ECC impairments, and environmental effects on proteins (heat up too much will denature them)

central fatigue

fatigue that occurs at or above the alpha MN (cortical, subcortical, spinal)

electrical fatigue

depolarization of the cells becomes diminshes as increasing number of APs sent down the t-tubules, which have only a small concentration of extracellular fluid, depletes its concentrations, “messing” up the concentration gradients and causing this

caffeine 

after continuous stimulation, the fibers begin to lose the ability to release calcium due to electrical fatigue, but adding a TON of this directly is able to stimulate the RyR receptors and increase the release again (also shows us that we haven’t run out of calcium stores in the SR)

central fatigue mechanism

feedback from metabolites (H+, lactate, etc) activates GrpIII/IV sensory neurons, which activate inhibitory inter-neurons, reducing MN firing and firing rates, force production, may signal pain/nociocieption/muscle damage

NMES (neuromuscular electrical stimulation)

mechanism that allow us to bypass central fatigue mechanisms and generate more force (not back to baseline max force tho) despite fatigue already setting in

basic adaptations to increase use 

hypertrophy, increase oxidative capacity, increased capillarization, transition from fast to slow fibers 

SAID (specific adaptation to imposed demand)

gains tend to be greatest for performance variables most similar to those related to the training, ex: if you train at one joint angle you will get strong at that angle and a little bit around it, but not so much at others, only what you activate will adapt!

time course of adaptation

accumulation of protein changes, largely a function of transcriptional activation, protein half life and exercise frequency

basic adaptations to decreased use

reduced size (atrophy), reduced oxidative capacity through decrease mitochondrial volume/number and decrease oxidative enzyme activity, slow to fast fiber transition (jury still out on capillarization)

basic adaptations to aging

reduced size, equivocal change on oxidative capacity, fast to slow fiber transition (jury still out on capillarization)

clinical goals of increasing muscular activity 

gain/regain functional independence, improve health and fitness, increase muscular strength/endurance, maximize athletic performance, performance changes that are task specific, increase strength and power (through CSA and/or neural drive), increase tolerance, increase muscle CSA 

changes in performance after training low rep (3-5 RM) training

see highest increase in 1 RM strength, but lowest repetitions of 60% RM 

changes in performance after high rep (20-28 RM) training 

see smallest increase in 1 RM, but highest repetitions of 60% RM

fiber type CSA increases across all fiber types

interestingly, in high rep exercise, see this trend across all fiber types after training

smallest change in CSA of fiber types

in low rep exercise, see this trend across all fiber types after training

most type I, medium IIa, low IIx

fiber type composition of distance runners, this is demonstrated by higher capillary length density, mitochondrial density, concentration of lipids within muscle, and sacroplasmic volume density

high type IIx, medium IIa, low I

fiber type composition in weight lifters, this is demonstrated by highest myofibrilar volume density (contractile fibers), fiber mean cross sectional area, decrease fat content within muscle

hypertrophy 

increase in size of existing muscle cells, most data suggest this as the mechanism at work for increasing muscle mass 

hyperplasia

increased number of new muscle cells, proposed mechanism is through “splitting” of muscle fibers

De Lorme (1940s) Human Exercise study

study on rehan of soldiers with knee injuries- proposed a strength-endurance continuum, a few reps against a heavy load increases strength/power, many reps against a light load increases muscular endurance

fast to slower myosin isoforms 

conversion of MHC with exercise follow this trend, generally, which takes longer and requires more intense training that changes in metabolic enzymes

Possible mechanims for change to slow to fast with training

study of scandinavian sprinters- training is characterized bu heavy resistance and intervals, tapering period when stop training before event, see an “overshoot” of fast fibers (small sample, results haven’t been replicated)

manifestations of decreased use 

reduced capacity for work, decreased force, power, endurance, increased fatigue, decrease in functional outcomes and QOL, altered task performance 

whole muscle changes with reduced muscle use

decrease muscle mass/CSA, especially with anti-gravity muscles (muscles with higher number of slow MHC tend to show greater atrophy than those with more fast MHC), decreased force, fiber type changes- contractile properties, alterations of muscle architecture (length, pennation, tendon/CT changes), metabolic alterations

slow soleas vs fast gastrocnemius

soleus shows faster atrophy with disuse than does gastroc

loss of mass/volume

muscle atrophy is typically a feature of this, may or may not be also relate to CSA

fiber atrophy 

specifically describes in terms of CSA, similar to whole muscle, this occurs in areas of greatest fiber populations (MUs) that are most often used 

summation of force

as disuse occurs and muscles transition from slow to fast, this causes problems with this since the more rapid a fiber is, the fast it falls from its peak, which will requires higher intensities in order to fuse tetanus

increased glycolytic enzyme activity

disuse causes this shift in enzyme activity, which is consistent with fiber type changes

oxidative enzyme activity with disuse 

mechanism is less clear, declines in both phasic and anti-gravity muscle have been observed (succinate dyhyrdogenase- SDH), in models with denervation component, no loss of SDH observed, even when MHC converts 

proteolysis

what atrophy is first driven by (during the first 5 days)

protein synthesis

what atrophy is mainly driven by after 2 weeks of disuse

downregulated translation

mechanism that is proposed to be the cause of reduction in synthesis of protein

3 main proteolytic pathways in muscle breakdown

• cathespins (lysosomal)

• calpains (calcium-dependent)

• ubiquitin-proteasome (ATP-dependent)

ubiquitin-proteasome pathway

where bulk of proteolysis occurs, ubuquitin binds to proteins to mark it for breakdown, then proteasome breaks up the protein into peptide fragments

calpain systems 

proteasome can’t degrade intact myofibrils, but rather only soluble actin and myosin, and since this system targets myofibrillar proteins, which will disrupt myofibrils, it may be needed for ubiquitin-proteosome action 

loss of strength > loss of mass

as we age, we see this pattern regarding strength and loss of mass, may be due to denervation/re-innervation as we lose some alpha MN and see compensatory larger MUs as a response, which decreases specific force

endurance training

exercise that older muscle responds better to (increased power and CSA) while young muscle responds the opposite way