Skeletal Muscle II

SR2002

Dr. Arimantas Lionikas

October 24, 2013

Muscle IIPlan

• Muscle Innervation• Neuromuscular transmission• Contractile properties• Electrical stimulation• Muscle fibre types

• Reading list: 1. Enoka R. Neuromechanics of human movement. 2002. Publishers: Human Kinetics, p. 257-278 2. MacIntosh, B.R., Gardiner, P.F. McComas, A.J. Skeletal muscle, 2nd edition. 2006. Publishers: Human Kinetics, p. 32-39, 126-150.3. McArdle W.D. et al. Exercise Physiology: energy, nutrition, human performance. 2001. Publisher: Lippincott Williams & Wilkins, p. p. 358-382.

Muscle Innervation

αMotor neuron

• One motor nerve innervates a group of muscle fibres

• Motor nerve divides into terminals that form neuromuscular junctions on muscle fibres

• Neuromuscular junctions are located in the middle of the fibres

Muscle Innervation (cont)

• Microscopic analysis: Three muscle fibres innervated by branches of a motor nerve

• Diphtheria toxin damages myelin sheaths of nerve fibres (shown by arrows)

Neuromuscular transmission

• Nerve fibres (axons) conduct action potentials (APs) at a fast rate (~40-80 m/s)

• Terminals of motor nerves form neuromuscular junctions (also called motor end plates)

• The key function of the neuromuscular junctions is transmission of activation from nerve to muscle fibres

Neuromuscular transmission• Arrival of the AP at the nerve

terminal triggers release of acetylcholine (Ach) into the synaptic cleft (space between nerve and muscle fibre)

• Ach is made from Ac-CoA from mitochondria and choline in nerve terminals

• Released Ach binds to receptors on the muscle fibre and triggers influx of Na+ followed by generation of action potential (AP) in muscle fibres

• Ach acts for a short time since it is degraded by Ach esterase enzyme

• Choline is taken up by nerve terminals for re-synthesis of Ach

Szule JA, Harlow ML, Jung JH, De-Miguel FF, et al. (2012)

Synaptic vesicles of axon terminals

Synaptic vesicles

The active zone

The process leading to the release of Ach involves docking of the synaptic vesicles to the active zone , fusion with the membrane and release of the mediator.

Neuromuscular transmissionClinical relevance

• Myasthenia gravis due to low levels of acetylcholine (Ach):

• Eyelids are dropped due to muscle weakness

• Injection of a drug which blocks Ach esterase helps to regain muscle strength: eyelids open

Before treatment After treatment • Myasthenia gravis

(autoimmune disease) can be due to low levels of:

• (1) acetylcholine (Ach) • (2) Ach receptor

• Drugs blocking neuromuscular transmission are muscle relaxants used during operations (ex.: suxamethonium)

• Tubocurorine is found in some plants. Indians used it in hunting (poisoned arrows)

• After depolarization of postsynaptic membranes, action potential (AP) is generated

• AP spreads to both ends of muscle fibresAction potential (AP)

Action potential (AP)

Contractile propertiesHuman muscles

• Contractile properties can be investigated in humans muscles

• Electrical stimulation is applied over surface electrodes

• Torque in isometric contraction is usually recorded

• The set up is for studies of the quadriceps muscle

Electrodes

Dynamometerstrap

Force

Muscle response to APSingle twitch contractions

ES

Twitch and Tetanus

Contractile propertiesHuman muscles

• Muscle force depends on the frequency of stimulation

• Unfused contractions are associated with fluctuation in force during a contraction

• Muscle fibres are activated at 5-100 Hz frequencies in voluntary contractions

• Electrical stimulation can be used for training of muscles

Westerblad et al. 2002

Role of Calcium: Tetanic contractions

• Continuous stimulation at 100 Hz causes a sustained increase in intracellular Ca2+ - [Ca2+]I and generates tetanic contractions (smooth contractions)

• [Ca2+]I matches force in repeated contractions

Isolated muscle fibre

• Muscle fibres were repeatedly stimulated at 100 Hz for 0.5 s each time

Westerblad et al. 2002

Applications of Electrical Stimulation• Neuromuscular electrical stimulation (NMES) is used for

functional and therapeutic applications in subjects with spinal cord injury or stroke.

A transcutaneous multichannel neuroprosthesis system allows persons with paraplegia unbraced ambulation for home andshort community distances. (Parastep I System User, courtesy of Sigmedic Inc., Fairborn, OH.)SHEFFLER & CHAE 2007

Muscle fibre types

• Skeletal muscle is not a homogeneous tissue.

• Muscle fibres that muscle consists of can be subdivided in two main types: type I and type II (the latter is further divided into IIA & IIX).

• Type of myosin heavy chains expressed in the fibres is the primary determinant of the fibre type and their contractile properties.

Mouse soleus. Acid preincubation pH 4.47

I IIA

Eriksson et al 2005

50 µm

Properties of fibre types

Characteristic Type I Type IIA Type IIX(B)

Morphology Fibre ∅ Small* Intermediate Large

Capillaries/mm2 High Intermediate Low

Mitochondrial vol High Intermediate Low

Histo- & Bio-chemistry

Myosin ATPase Low High High

Glycolytic capacity Low High High

Oxidative capacity High High/Medium Low

Contractility Contraction Slow Fast Fast

Relaxation Slow Fast Fast

Fatigue resistance High Moderate/High Low

Adaptation# Increase in fibre area Low Moderate Moderate

* Not always; depends on the muscle. Size between type I and II is about the same in soleus# Adaptation to several weeks of strength training.

Fibre type distribution in various muscles• Proportion of fibre types differ among muscles.• Type I fibres dominate in postural muscles (e.g.

soleus) and muscles involved in fine movements (e.g. adductor pollicis).

• Type II fibres dominate muscles involved in movements requiring quick and / or powerful contractions (e.g. orbicularis oculi, biceps brachii).

Harridge, Bottinelli et al. 1996

120 ms

68 ms

81 ms

Muscle % type I

Orbicularis oculi 15

Tricep brachii 37

Quadriceps femoris 52

Adductor pollicis 80

Soleus 80

Variation in fibre types among individuals

• Even though on average vastus lateralis muscle consists of ~50 of type I fibres, there is a broad range of variation between individuals (from ~20% to >80% of type I fibres).

• Important consequences of variation of fibre type composition:– Prevalence of certain fibre type is favourable for some athletic

activities (e.g. type I – endurance events, type II – speed and power events).

– Apparently increasing proportion of type II fibres is associated with prevalence to weight gain and cardiovascular risk.

Factors affecting proportion of fibre types• Genetic factors play important role in proportion of fibre types.• Moderate changes may occur as adaptation to physical activity or

lack of it.• Drastic change in degree of activity leads to marked shift in

proportion of fibre types.

Type IIType I

Endurance TrainingImmobilization

Spinal Cord Injury

Proportion of Fibre Types

Muscle IISummary

• One motor nerve innervates many muscle fibres

• Acetylcholine plays a key role in transmission of excitation from nerve to muscle

• For muscle contraction to occur release of calcium from sarcoplasmic reticulum is required

• Proportion of type I and type II fibres are important determinants of contractile properties.