L19 MSK Physiology 5 Muscle performance

Overview

This is the fifth lecture in the neurons-to-muscle series, and it moves from how a muscle fibre is made to contract to how much force a whole muscle actually produces. It has three parts. First, the intrinsic limits on performance: the metabolic and contractile properties of the three fibre types, and the mechanical relationships between force and length and between velocity and load, which mean that the same neural signal produces different output depending on the muscle’s current state, so the brain needs proprioceptive feedback. Second, the anatomical unit of motor control, the motor unit, and why its size determines both its force output and how easily it is recruited. Third, the two mechanisms the nervous system uses to grade force, frequency (rate) modulation within a unit and recruitment of additional units, plus how training changes what the muscle can do.

Recap: from excitation to contraction

The preceding lectures established the pathway that this lecture builds on:

• Lectures 1 and 2: neurons and nerves (dendrites, soma, axons, synapses); the resting membrane potential, set by the ratio of [Ion]out/[Ion]in and by permeability and conductance; gated ion channels including voltage-gated Na+ channels, K+ channels, mechanically and ligand-gated variants, and the Na+/K+-ATPase; passive (local) potentials, which are graded and decay with distance and time (EPSPs and IPSPs); and the action potential, with threshold and absolute and relative refractory periods.
• Lecture 3: propagation of action potentials by myelination, nodes of Ranvier and saltatory conduction, with larger diameter giving faster conduction; and the chemical synapse (presynaptic [Ca2+]i, vesicle fusion, transmitter release; postsynaptic ionotropic and metabotropic receptors).
• Lecture 4: the neuromuscular junction as a synapse using ACh and acetylcholinesterase, where action potentials are transmitted one for one; the structural hierarchy of skeletal muscle (whole muscle, fasciculus, fibre, myofibril, sarcomere) with the sarcoplasmic reticulum and t-tubule network; and excitation-contraction coupling, driven by actin-myosin interaction, Ca2+ and ATP. [figure attribution on the recap slide is partly obscured by an overlying micrograph]

Excitation-contraction coupling in skeletal muscle, in order:

1. The action potential enters the t-tubules.
2. Depolarisation of the t-tubule membrane activates the DHP protein, which opens the RYR channel in the sarcoplasmic reticulum.
3. Ca2+ leaves the SR down its concentration gradient.
4. Ca2+ binds troponin, moving tropomyosin off the binding sites.
5. The cross-bridge cycle is activated and force is generated.
6. Ca2+ is pumped back into the SR by the SERCA pump.
7. Tropomyosin moves back onto the binding sites and the muscle relaxes.

Steps 4 and 7 are the forward and reverse arms of the same reversible step at the thin filament.

Fibre types

Humans and most mammals have a mixed distribution of fibre types, and the three types are intermingled within a single muscle rather than segregated into separate regions.

Type I, slow oxidative

• Slow form of myosin ATPase.
• Many mitochondria, high levels of oxidative enzymes, rich blood supply.
• Slow form of SERCA.
• Single twitch is low and broad, rising and falling slowly over roughly 100 ms.
• Under tetanic stimulation force rises to a plateau and is maintained for about 60 minutes before declining, i.e. fatigue resistant.
• Energy supply: myoglobin delivers O2 to mitochondrial oxidative enzymes, which use free fatty acids and glucose as substrate; ATP is regenerated from ADP slowly but the supply is sustained. Contraction is slow but sustained.

Type IIB, fast glycolytic

• Fast form of myosin ATPase.
• Few mitochondria, low levels of oxidative enzymes, fewer capillaries.
• Fast form of SERCA.
• Single twitch is tall and narrow, rising and falling rapidly, complete well within 100 ms.
• Under tetanic stimulation force rises quickly to a peak then falls away over about 5 minutes despite continued stimulation, i.e. it fatigues.
• Energy supply: glycolytic enzymes in the cytosol acting on glucose and glycogen produce large amounts of ATP quickly, but glycogen stores are limited and fast use exhausts them, so the supply runs out.

Type IIA, intermediate

• Fast form of myosin ATPase.
• Mix of oxidative and glycolytic enzymes.
• Intermediate speed and intermediate fatigability.

Mechanical limits to performance

Two relationships set the mechanical ceiling on what a muscle can do.

Velocity-load relationship. Velocity of shortening is maximal at zero or low load and falls steeply as load increases, flattening towards zero velocity at high load. The relationship is inverse: heavier loads are moved more slowly.

Length-tension relationship. Active tension follows an inverted U: it is low at short lengths, rises to a peak at an optimum length within the physiological range, and falls again at long lengths. This tracks the degree of overlap between thick and thin filaments at short, optimal and stretched sarcomere lengths. Passive tension is near zero at short lengths and rises progressively as the muscle is lengthened.

Why these matter. For a given motor control signal, the velocity and the tension actually achieved depend on the load and on the muscle’s length. Both relationships operate at the same time: plotted as a surface with force against length and velocity, the length-tension curve is the slice at zero velocity and the force-velocity curve is the slice at optimum starting length, so any combination of current length and velocity gives a different force for the same neural drive. The velocity axis spans both lengthening and shortening.

Because output depends on starting length and current velocity, the brain cannot predict the force a given command will produce unless it knows those starting conditions and receives feedback about achieved output. This is what makes proprioceptive feedback necessary for control.

Proprioceptive feedback

The required length and velocity information is supplied by the muscle spindle, a sensory organ made up of modified muscle fibres. The spindle lies in parallel among the extrafusal fibres, and the Golgi tendon organ sits at the musculotendinous junction. Structures labelled on the proprioceptor diagram: tendon, capsule, Golgi tendon organ, perimysium of the muscle fibre bundle, connective tissue capsule, extrafusal muscle fibres, intrafusal fibres (nuclear bag fibres and nuclear chain fibres), type Ib sensory fibre, type Ia sensory endings, type II sensory endings, and efferent motor fibres to the spindle and to the extrafusal fibres.

Transcript flag: the efferent-fibre labels on this figure were very small at slide resolution. The alpha efferent motor fibre is legible; the other efferent Greek letter was read as best as possible and may be gamma rather than delta.

Effects of training

Strength training

• More actin and myosin, so increased fibre diameter (hypertrophy).
• More cross-bridges, so more force.

Endurance training increases oxidative capacity and therefore the ability to sustain activity:

• More mitochondria, and so more enzymes.
• More capillaries and more myoglobin.
• Increased muscle stores of lipid.
• Increased ability to use lipids directly from the blood.

The motor unit

A motor unit is a single motor neuron together with all of the muscle fibres that neuron innervates. Its properties:

• All the muscle fibres in one unit are of the same metabolic type.
• Unit size varies from small (about 6 fibres) to large (more than 2000 fibres).
• All the fibres in a unit are active at once, so the maximum force a unit can produce depends on its size.
• The size of the motoneuron cell body depends on the number of muscle fibres in the unit.
• The fibres of one motor unit are intermingled with those of other units within the muscle rather than grouped together.

Why size determines recruitment order. The nerve cell body size reflects the number of fibres innervated. Synaptic input arrives from the motor cortex, and the action potential is initiated at the axon hillock, which has an increased density of Na+ channels. A larger neuron needs more input to reach threshold, so a larger motor unit means a larger cell body and therefore more synaptic input is needed for recruitment. The mechanism is electrical: larger neurons have lower input resistance, so each synaptic input produces less voltage change because more current is lost through leak and capacitance, and more inputs are therefore needed to reach action potential threshold. By Ohm’s law $I\times R=V$, so $I\times 2R=2V$: for the same current, halving the resistance halves the voltage change.

Control of force: frequency modulation

Force is regulated by two mechanisms: frequency modulation, which changes the rate of action potential activity in each motor unit, and recruitment, which changes the number of motor units generating tension.

Frequency (rate) modulation changes the force produced by an individual motor unit, and works by mechanical summation of twitches:

• A single stimulus gives one isolated twitch.
• At a low rate of stimulation the twitches remain discrete but each successive peak sits higher than the last (unfused summation).
• At higher frequency the twitches partially fuse and force oscillates around a higher level.
• Above the fusion frequency the twitches merge completely into a smooth trace that rises steeply and plateaus at the maximum obtainable force, a tetanic contraction.

So higher frequency gives higher force, up to a limit, and this mechanism provides the finer control of the two.

Mechanisms of the force increase:

• The initial twitch expends energy stretching the muscle; later twitches work on an already stretched muscle and so contribute more force to the tendon.
• At high rates, intracellular [Ca2+] rises, increasing actin-myosin interaction.

Control of force: recruitment

Recruitment regulates the number of motor units generating tension: more units means more force. Activity starts with the smaller, fatigue-resistant units, and larger units are recruited as more force is needed. On a plot of total muscle force over time, unit 1 firing alone gives a low steady force, and when unit 2 is recruited total force steps up to a new higher plateau.

• Recruitment is probably the most important force-regulation mechanism.
• Size principle of motor unit recruitment: recruitment is orderly, smallest to largest.
• Because small units are recruited first they are more tonically active, and this gives fine graded control of small forces.
• Bigger units are automatically recruited as the required force increases.

Self-test

1. List the features of a type I slow oxidative fibre given in the lecture, covering its myosin ATPase, mitochondria and blood supply, and SERCA.
2. Describe the shape and duration of a single twitch in a type I fibre and in a type IIB fibre, and state how long each sustains force under tetanic stimulation.
3. Distinguish type IIB from type IIA fibres.
4. Explain why type IIB fibres fatigue within about 5 minutes while type I fibres sustain force for about 60 minutes.
5. Describe the excitation-contraction coupling sequence in skeletal muscle, in order, from the arrival of the action potential to relaxation.
6. Describe the velocity-load relationship.
7. Describe how active and passive tension each vary with muscle length, and state where active tension peaks.
8. Explain why the brain needs information about a muscle’s current length and velocity in order to control it.
9. Explain how the three-dimensional force-length-velocity surface relates to the length-tension and force-velocity curves.
10. Name the sensory organ that supplies length information and state where it lies relative to the extrafusal fibres. Name the other proprioceptor shown and its location.
11. Distinguish the adaptations produced by strength training from those produced by endurance training.
12. Define a motor unit and list its properties as given in the lecture, including the range of unit sizes.
13. Explain why a larger motor unit requires more synaptic input to be recruited.
14. Describe how force from a single motor unit changes as stimulus frequency is increased from a single stimulus to above the fusion frequency.
15. Explain the two mechanisms by which repeated stimulation increases the force a motor unit delivers.
16. State the size principle of motor unit recruitment and explain what functional advantage it gives at low force levels.
17. Distinguish frequency modulation from recruitment as mechanisms of force control, including which gives finer control and which the lecture calls the most important.
18. A sprinter and a marathon runner train for their events. Predict, from the training adaptations described, which fibre-level and tissue-level changes each would be expected to show.
19. A muscle is held at a length near the short end of its physiological range and asked to move a heavy load. Predict what happens to the force and the velocity achieved compared with the same neural command at optimum length and light load, and explain why.
20. Integrative: a person picks up a very light object and then a heavy one with the same limb. Explain, using fibre types, motor unit size and both force-control mechanisms, how the nervous system grades the force between these two tasks.

Answers

Reveal answers

1. Slow form of myosin ATPase; many mitochondria, high levels of oxidative enzymes, rich blood supply; slow form of SERCA.
2. Type I: a low, broad twitch rising and falling slowly over roughly 100 ms; under tetanic stimulation force plateaus and is maintained about 60 minutes before declining. Type IIB: a tall, narrow twitch rising and falling rapidly, complete well within 100 ms; under tetanic stimulation force peaks then falls away over about 5 minutes.
3. Both have the fast form of myosin ATPase. Type IIB is glycolytic, with few mitochondria, low oxidative enzymes and fewer capillaries, and a fast SERCA. Type IIA has a mix of oxidative and glycolytic enzymes and is intermediate in speed and fatigability.
4. Type IIB relies on cytosolic glycolytic enzymes using glucose and glycogen: ATP is made quickly and in large amounts but glycogen stores are limited and are used fast, so supply runs out. Type I uses myoglobin-delivered O2 and mitochondrial oxidative enzymes with free fatty acids and glucose as substrate: ATP is regenerated slowly but the supply is sustained.
5. (1) AP enters the t-tubules. (2) Depolarisation of the t-tubule membrane activates the DHP protein, which opens the RYR channel in the SR. (3) Ca2+ leaves the SR down its concentration gradient. (4) Ca2+ binds troponin, moving tropomyosin off the binding sites. (5) The cross-bridge cycle is activated and force is generated. (6) Ca2+ is pumped back into the SR by SERCA. (7) Tropomyosin moves back onto the binding sites and the muscle relaxes.
6. Velocity of shortening is maximal at zero or low load and falls steeply as load increases, flattening towards zero velocity at high load: an inverse relationship.
7. Active tension is an inverted U: low at short lengths, peaking at an optimum length within the physiological range, and falling again at long lengths, following thick-thin filament overlap. Passive tension is near zero at short lengths and rises progressively as the muscle is lengthened.
8. For a given motor control signal, the velocity and tension achieved depend on the current load and length, so the same command produces different output in different states. The brain therefore needs to know the starting conditions and to receive feedback about achieved output in order to choose the right control signal.
9. Force is plotted against length and velocity as a surface. The length-tension curve is the slice through that surface at zero velocity; the force-velocity curve is the slice at optimum starting length. Both relationships act simultaneously, so each combination of length and velocity gives a different force for the same neural drive.
10. The muscle spindle, made of modified muscle fibres, lying in parallel among the extrafusal fibres. The other proprioceptor is the Golgi tendon organ, at the musculotendinous junction.
11. Strength training: more actin and myosin, so increased fibre diameter (hypertrophy), and more cross-bridges, so more force. Endurance training: increased oxidative capacity, via more mitochondria and enzymes, more capillaries and myoglobin, increased muscle lipid stores and increased ability to use lipids directly from the blood, giving greater sustained activity.
12. A single motor neuron and all the muscle fibres it innervates. All fibres in a unit are of the same metabolic type; size ranges from about 6 fibres to more than 2000; all fibres in a unit are active at once so maximum unit force depends on size; motoneuron cell body size depends on the number of fibres in the unit; the fibres of one unit are intermingled with those of other units.
13. A larger unit has a larger cell body, and larger neurons have lower input resistance, so each synaptic input produces less voltage change because more current is lost through leak and capacitance. More synaptic inputs are therefore needed to reach action potential threshold at the axon hillock.
14. A single stimulus gives one isolated twitch. At low stimulation rates the twitches stay discrete but each peak is higher than the last (unfused summation). At higher frequency they partially fuse and force oscillates around a higher level. Above the fusion frequency they merge into a smooth trace that plateaus at the maximum obtainable force, a tetanic contraction.
15. The initial twitch expends energy stretching the muscle, so later twitches act on an already stretched muscle and deliver more force to the tendon; and at high rates intracellular [Ca2+] rises, increasing actin-myosin interaction.
16. Recruitment is orderly, from smallest unit to largest. Small units are recruited first and so are more tonically active, which gives fine graded control of small forces; larger units are added automatically as required force rises.
17. Frequency modulation changes the rate of action potential activity within each motor unit, so more APs give more force, up to a limit, and it provides the finer control. Recruitment changes the number of active motor units, so more units give more force, following the size principle, and it is probably the most important force-regulation mechanism.
18. The sprinter, training for strength, would be expected to gain actin and myosin with increased fibre diameter (hypertrophy) and more cross-bridges producing more force. The marathon runner, training for endurance, would be expected to gain oxidative capacity: more mitochondria and oxidative enzymes, more capillaries and myoglobin, greater muscle lipid stores and greater use of blood lipids, supporting sustained activity.
19. Force would be lower and velocity would be lower. Active tension is reduced at short lengths because of the length-tension relationship, and velocity of shortening falls steeply as load increases because of the velocity-load relationship. Both act at the same time, so the same neural command yields a different point on the force-length-velocity surface.
20. For the light object, few and small motor units are recruited, firing at low rates; because small units are recruited first under the size principle and their fibres are fatigue-resistant, force is small and finely graded. As the load increases, the firing rate within active units rises so their twitches summate towards fusion, and progressively larger units, containing more fibres and faster more glycolytic fibre types, are recruited, each addition stepping total muscle force up. The combination of rate modulation for fine adjustment and recruitment for large increments spans the full force range.