Muscle tissue

Abstract

Muscle tissue is largely composed of actin (thin) and myosin (thick) filaments, which work in a coordinated effort to generate force and, in turn, muscle contraction. Depending on the intracellular arrangement of these myofilaments, muscle tissue is classified as either striated (skeletal and cardiac) or nonstriated (smooth) muscle. The myofilaments of striated muscle are arranged into sarcomeres; smooth muscle lacks this arrangement. Although the different types of muscle follow very similar principles on a molecular level (sliding filament mechanism), their functions vary greatly. Skeletal muscle is attached to the skeleton and provides voluntary movement. Smooth muscle possesses greater elasticity and is primarily found in the walls of hollow internal organs, where it contracts and relaxes involuntarily to fulfill a wide range of functions. In the intestine, for example, smooth muscle is responsible for transporting the bolus, whereas in the blood vessels it is primarily responsible for ensuring vascular resistance in circulation.

Muscle cells (myocytes)

Overview

  • Function: produce a contraction or generate tension
  • Origin: mesoderm
  • Histological classification
    1. Striated muscle fibers
    2. Smooth muscle fibers:
      • Walls of hollow organs: e.g., stomach, bladder, and uterus
      • Walls of arteries and veins
      • Respiratory, urinary, and reproductive tracts

Muscle cell structures

Muscle cell structure Characteristics
Sarcolemma
Sarcoplasm
  • Serves as the cytoplasm of striated muscle cells
  • Notable contents:

Sarcoplasmic reticulum (SR)

Myofilaments
  • Protein fibers consisting of thick (myosin) and thin (actin) filaments
  • Achieve contraction through their interaction together, which is regulated by special proteins such as troponin

Types of skeletal muscle fibers

Type 1 fibers (e.g. postural muscles) Type 2 fibers (extraocular muscles)
Appearance
Energy production
  • Predominantly from anaerobic glycolysis
Myosin ATPase activity
  • Low
  • High
Contraction velocity
  • Slow-twitch
  • Fast-twitch
Activity period
  • Long-term activity
  • Short-term activity

Structural differences between muscle cell types

Skeletal muscle Cardiac muscle Smooth muscle
Cell morphology
  • Large elongated cells with multiple nuclei located at the periphery
  • Branched cells with a central nucleus
  • Spindle-shaped with a central nucleus
Invaginations of the sarcolemma

Arrangement of myofilaments

Myofilaments are protein fibers consisting of thick (myosin) and thin (actin) filaments.

Types

Actin myofilaments

Myosin filaments

  • Function: Thick filament that slides along actin filaments, which is driven by ATP hydrolysis
  • Structure
    • Myosin filaments contain ∼ 300 myosin molecules.
    • The myosin molecule is composed of a tail and a head, which are formed from several heavy and light chains depending on the myosin type.
      • Myosin heads have an affinity both for actin and ATPase activity.
      • The heavy chains are wound around each another in a coil-like structure, with myosin heads protruding on both sides.

Both striated and smooth muscle cells mediate contractions via actin and myosin!
The structure of troponin complex proteins differs slightly in cardiac and skeletal muscles. In myocardial infarction, cardiac myocytes are damaged as a result of absolute oxygen deficiency and release their intracellular content into the bloodstream. An increase in cardiac troponin levels in blood indicates cardiac muscle tissue damage.

Two types of arrangement of myofilaments

  • Smooth muscle: disorganized
  • Striated muscle: sarcomere

Sarcomeres of striated muscle

During muscle contraction:
- Thick (myosin) and thin (actin) filaments DO NOT shorten in length.
- A bands remain the same length
- Z lines come closer together
- I bands and H zone decrease in size.

Myofilament contraction

At resting position, actin and myosin are unable to interact because they are inhibited by regulatory proteins (e.g., tropomyosin), which require an initiating stimulus to undo.

Initiation of muscle contraction

Skeletal muscle contraction results from an increase in intracellular calcium from stores in the sarcoplasmic reticulum. This explains the ability of skeletal muscle to contract despite treatment with calcium channel blockers, which can block an influx of extracellular calcium through DHPRs but cannot affect DHPR voltage-sensing capabilities and the resulting intracellular calcium release.

Steps of the contraction cycle (sliding filament theory)

  1. Orientation of the myosin head: hydrolysis of ATP to ADP and Pi (both remain on the myosin head)myosin head alters its confirmation (“cocked state”)it is ready to bind actin once
  2. Crossbridge formation: intracellular calcium binds troponin and causes a conformational change → moves tropomyosin out of the myosin binding site on actinmyosin head binds actin at a 90° angle, forming a crossbridge
  3. Powerstroke of the myosin head: Myosin head releases ADP and Pi → myosin head turns by 45°, pulling myosin along actin → muscle shortens
  4. Loosening of the crossbridge: ATP binds myosin headdetaches from the actin filamentmyosin head returns to its starting position
  5. Replication of the cycle: If calcium concentration in the muscle cell remains elevated → a new cycle begins with reorientation of the myosin head.
    • Depending on ATPase activity (ATP cleavage rate per unit of time) of the heavy myosin chain, there may be ∼ 10–100 crossbridge cycles per second.
    • The more crossbridge cycles per unit of time, the faster and stronger the contraction.


When a person dies and breathing and circulation stop, muscle cells lack oxygen and cannot use aerobic respiration to efficiently produce ATP anymore. Without ATP, the crossbridges between myosin and actin filaments cannot be resolved and muscles become tense, which is referred to as rigor mortis.References:[1][2][3][4]

Energy provision for muscle contraction

ATP is required by muscle cells as an energy source for:

  • Maintaining structure and ion gradients
  • Interaction between the myosin head and actin that leads to muscle contraction

Sources of ATP synthesis

  • Storage of ATP is very limited and requires reproduction.
  • The source of ATP reproduction depends on the energy demands of the activity.
  • ATP ultimately derives from nutritional sources
Source Characteristics Calories (kcal/g)
Protein
  • 4 kcal/g
Glucose
  • Short term reservoir of energy
  • Can be stored as glycogen
Fat
  • 9 kcal/g

Aerobic sources

  • Main sources when energy demand does not override the availability of oxygen for ATP creation (e.g., walking)
  • Formed from oxidative formation via the citric acid cycle and respiratory chain from metabolic products of either:

Anaerobic sources

Anaerobic glycolysis

  • Main source when energy demand overrides the availability of oxygen for ATP creation (e.g., sustained sprint)
  • Glucosepyruvatelactic acid + 2 ATP
  • Does not require oxygen → can continue even when energy demand exceeds oxygen supply
  • See anaerobic glycolysis for more information.

Creatine phosphate

In addition to the ATP supply, creatine phosphate is an important short-term energy store in the muscle cell!

The creatinine concentration in urine is proportional to the glomerular filtration rate.

Adenylate kinase (myokinase)

  • Another anaerobic form of immediate ATP reproduction
  • An enzyme of the mitochondrial intramembrane space transfers a phosphate residue from one ADP to the other, which makes ATP available (ADP + ADPATP + AMP)

Glucose-alanine cycle (Cahill cycle)

  • Definition: metabolic cycle in which alanine (from protein degradation) is transported from skeletal muscle to the liver and receives glucose in exchange for energy production
  • Key enzyme: alanine aminotransferase (ALT)
  • Process
    1. Alanine is released during muscle protein degradation.
    2. Alanine is transported by blood to the liver, where it is transaminated to pyruvate by the enzyme alanine aminotransferase (ALT).
    3. Gluconeogenesis is responsible for the conversion of pyruvate to glucose, which is released in blood and transported to the muscle.
    4. Glucose can be degraded in the muscle, serving as a source of energy.
  • A byproduct of energy production from alanine is production of urea (consumes a lot of energy).
  • Pathway usually only used in states of muscle breakdown (catabolism)

The glucose-alanine cycle does not result in the organism gaining energy in the thermodynamic sense, but serves to provide muscles with glucose!

Lactic acid cycle (Cori cycle)

  • Definition: metabolic cycle in which lactate (from anaerobic glycolysis in muscle) is transported to the liver, where it is converted into glucose, which is transported back to the muscles for energy production
  • Key enzyme: lactate dehydrogenase (LDH)
  • Process
    1. In the absence of oxygen in active skeletal muscle, LDH catalyzes the reduction of pyruvate to lactate (anaerobic glycolysis).
    2. Lactate is transported within the blood to the liver, where it is converted into pyruvate by the enzyme LDH.
    3. Pyruvate serves as the source of gluconeogenesis: it is converted into glucose and transported to the muscle.
    4. Glucose can be degraded in the muscle, serving as a source of energy.

Comparison of muscle tissue types

Comparison of contractile filaments

Skeletal muscle/cardiac muscle Smooth muscle
Organization/orientation Sarcomere Disorganized
Interaction with calcium Troponin Calmodulin
Myosin binding site blockage Tropomyosin Tropomyosin with caldesmon and calponin
Anchorage Z lines (skeletal muscle)/intercalated discs (cardiac muscle) Dense bodies
Phosphorylation of the light myosin chain required No Yes

Comparison of stimulation and contraction

Skeletal muscle Cardiac muscle

Smooth muscle

Initiating structure or stimulus
  • Alpha motor neuron via motor endplates
  • Cardiac pacemaker cells
  • Hormones (especially from autonomic neurons
  • Pacemaker cells
  • Metabolic factors (e.g., pH value)
  • Mechanical stimulus (e.g., stretching of a sphincter)
Special features of electromechanical coupling
  • Calcium-induced calcium release
  • No action potential required for contraction
  • Calcium influx in the cell, especially from the extracellular space
  • The light myosin chains require phosphorylation for interaction with actin.
Function as a unit
  • All skeletal muscle fibers must be stimulated individually by their motor endplate.
  • Two types: single-unit and multi-unit
    1. Single-unit smooth muscle cells are connected via gap junctions and mutually contract (functional syncytium).
    2. Multi-unit smooth cells are separate and must also be stimulated separately.

Clinical significance

  • 1. Catterall WA. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011; 3(8): p. a003947. doi: 10.1101/cshperspect.a003947.
  • 2. Opie LH. Pharmacological differences between calcium antagonists. Eur Heart J. 1997; 18: pp. A71–9. pmid: 9049541.
  • 3. Dayal A, Schrötter K, Pan Y, Föhr K, Melzer W, Grabner M. The Ca2+ influx through the mammalian skeletal muscle dihydropyridine receptor is irrelevant for muscle performance. Nat Commun. 2017; 8(1). doi: 10.1038/s41467-017-00629-x.
  • 4. Striessnig J, Bolz HJ, Koschak A. Channelopathies in Cav1.1, Cav1.3, and Cav1.4 voltage-gated L-type Ca2+ channels. Pflugers Arch. 2010; 460(2): pp. 361–74. doi: 10.1007/s00424-010-0800-x.
last updated 11/18/2018
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