Muscle tissue

What is muscle tissue important for ?

Movements of the body

→ it is characterised by aggregates of specialised, elongated cells arranged in parallel array that have primary role of contraction

What types of myofilaments are there ?

1. Thin filaments - composed primarily of the protein actin, each thin filament of fibrous actin (F-actin) is a polymer primarily formed from globular actin molecules (G-actin)

2. Thick filaments - composed primarily of protein myosin II, each thick filaments consists of myosin II molecules, the long rod-shaped tail. portion of each molecule aggregates in a regular paralleled but staggered array, whereas the head portions project out in a regular helical pattern

Where can we find the 2 types of myofilaments ?

They occupy the bulk of cytoplasm which in muscle cells is called sarcoplasm

What do muscle cells contain?

A large number of aligned contractile filaments that the cells use for the single purpose of producing mechanical work

Where can we also find actin and myosin ?

In other cell types where they play a key role in cellular activities, such as cytokinesis, exocytosis and cell migration

What are muscles classified by?

The appearance of the contractile cells

By what are the striations made ?

By the specific architectural arrangement of both thin and thick myofilaments, this arrangement is the same in all types of striated muscle cells

What is the main difference between skeletal muscle cells and cardiac muscle cells ?

In their size, shape and organisation relative to one another

What is the difference between the muscle fibers and the connective tissue fibers ?

Muscle fibers are are skeletal muscle cells

Connective tissue fibers are extracellular products of connective tissue cells

what does the sarcolemma consist of ?

Of the plasma membrane of the muscle cells, its external lamina and the surrounding reticular fibers

What do we find around individual muscle fibers and bundles of muscle fibers ?

Connective tissue essential for force transduction

→ at the end of the muscle the connective tissue continues as a tendon or other arrangements of collagen fibers that attaches the muscle

→ a rich blood supply of blood vessels and nerves travels in the connective tissue

What is the connective tissue around the muscle named according to ?

According to its relationship with the muscle fibers

1. Endomysium

2. Perimysium

3. Epimysium

What are fascicles ?

They are functional units of muscle fibers that tend to work together to perform a specific function

What are skeletal muscle fibers characterised by ?

By speed of contraction, enzymatic velocity and metabolic activity

• classified based on contractile speed and enzymatic velocity of the fibers myosin ATPase reaction and metabolic profile

What does the contractile speed determine ?

How fast the fibers can contract and relax

What does the velocity of myosin ATPase reaction determine ?

The rate at which this enzyme is capable of breaking down ATP molecules furring the contraction circle

What does the metabolic profile indicate ?

The capacity for ATP production by oxidative phosphorylation or glycolysis

• fibers characterised by oxidative metabolism contains large amounts of myoglobin and an increased number of mitochondria→ with they constituent cytochrome electron transport complexes

What is myoglobin ?

It is a small globular oxygen binding protein that contains a ferrous form of iron, it resembles hemoglobin in the erythrocytes and is found in various amounts in muscle fibers

• myoglobin functions primarily to store oxygen in muscle fibers and provides a ready source of oxygen for muscle metabolism

What is a muscle fiber filled with ?

With longitudinally arrayed structural subunits called myofibril, they are visible in favourable histologic preparations and are best seen in cross sections of muscle fibers → in these sections they give a fiber strippled appearance

How are myofibrils arranged ?

They extend the entire length of muscle cells

What are myofilaments ?

They are individual filamentous polymers of myosin II and actin and its associated proteins (thin filaments)

→ actual contractile element of striated muscle

• the bundles of myofilaments that make up the myofibril are surrounded by well developed, smooth surfaced endoplasmic reticulum also called sarcoplasmic reticulum

How is sarcoplasmic reticulum organised ?

It forms a highly organised tubular network around the contractile elements in all striated muscle cells - mitochondria and glycogen deposits are located between the myofibrils in association with the sER

Where can we see cross striations?

They are evident in H+E stained preparation of longitudinal sections of muscle fibers, may also be seen in unstained preparations of living muscle fibers examined with a phase contrast or polarising microscope in which they appear as alternating light and dark bands

what are the light and dark bands named ?

A band and the I band

A band = dark band

I band = light band

What happens to the light I band ?

It is bisected by a dense line, the Z line also called the Z disc

What happens to the dark A band ?

It is bisected by a less dense or light region called the H band

→ further dissecting this we find a narrow dense line called the M line

What is the cross banding pattern of the striated muscle a result of ?

Of the arrangement of the 2 kinds of myofilaments

What does the Z matrix include ?

It includes a number of proteins that anchor Z lines to that of neighbouring myofibrils and to adjacent cell membrane

What is myosin II ?

It’s shaped actin associated motor protein, its a dimer composed of 2 heavy polypeptide chains and 4 light chains

• has 2 globular heads that are connected via lever arms with a long tail

• each monomer contains one essential light chain and one regulatory light chain that are wrapped around the lever arm region just below the myosin head

• each globular myosin head represents a heavy chain motor domain that projects at one inch of the myosin molecule

• myosin head has 2 specific binding sites → once for ATP with ATPase activity and for actin

What do regulatory light chains stabilise ?

The lever arms

What determines the speed and strength of muscle contraction ?

The interactions between the heavy and light chains

What does enzymatic digestion of myosin produce ?

2 fragments: a heavy meromyosin and light meromyosin

• The HMM consist of the heads, lever arms and both pairs of light chains

• The LMM consists of the tail

How do myosin molecules in striated muscle aggregate ?

Tail to tail to form bipolar thick myosin filaments: the tail segments overlap so that the globular heads project from the thick filament

→ the bar zone in the middle of the filament does not have a globular projections, thick filaments are connected to each other at their bare zone by a family of M line proteins

What do accessory proteins do ?

They maintain efficient and speed of muscle contraction both thick and thin filaments in each myofibril must be aligned precisely and kept at an optimal distance from one another

→ they are essential in regulating the spacing, attaching and alignment of the myofilaments

What happens during muscle contraction?

The sarcomere and I band shortens, whereas the A band remains the small length to maintain the myofilaments at a constant length → the shortening of the sarcomere must be caused by an increase in the overlap of the thick and thin filaments. → This overlap can be seen by comparing EM of resting and contracts muscle → The H band narrows and the thin filaments penetrate the H band during contraction → these observations indicate that the thin filaments slide past the thick filaments during contraction

What prevents the myosin heads to bind to actin molecules in resting muscles?

Tropomyosin, it covers the myosin binding site on actin molecules

What initiates muscle contraction ?

Nerve stimulation

What is the actomyosin cross bridge cycle ?

It is a series of coupled biochemical and mechanical events

→ myosin as an actin associated motor protein with ATPase activity, converts the chemical energy into mechanical force by cycling between actin attached and actin-detached stages during its ATPase cycle.

→ each cross bridge consists of 5 stages: releases, bending, force generation and reattachment

!!!!In cardiac muscle, relative durations of individual stages may be altered by changes in molecular composition of tissue specific myosin molecules - but the basic cycle is believed to be the same for all myosin-actin interactions

By what is muscle contraction regulated ?

By Ca2+ → it must be available for the reaction between actin and myosin to occurs

→ and must be remove after contraction

By what is the rapid delivery and removal of Ca2+ regulated ?

By the sarcoplasmic reticulum and the transverse tubular system

What does the terminal cisternae contain ?

Its plasma membrane contains an abundance of gated Ca2+ release channels called ryanodine receptors which are involved in releasing Ca2+ in the sarcoplasm

What is the transverse tubular system - T system ?

Consists of numerous tubular invaginations of the plasma membrane, each one is called a T tubule

• these penetrate to all walls of the muscle fiber and are located between adjacent terminal cisternae at the A-I junction

• they contain voltage-sensor proteins which are depolarisation-sensitive transmembrane channels that are activated when the plasma membrane depolarises

• Conformational changes of these proteins directly affect gated Ca2+ release channels located in the adjacent plasma membrane of the terminal cisternae

What is a triad structure ?

Its the complex of one T tubule and 2 adjacent terminal cisternae

→ found in skeletal muscle at the level of A-I junctions

→ are important elements for coupling extracellular events with intracellular responses that lead to muscle contraction

What triggers Ca²⁺ release in muscle contraction?

Voltage sensors in T-tubules activate ryanodine receptors (RyR) in the sarcoplasmic reticulum.

Where does the Ca²⁺ come from during muscle contraction?

Sarcoplasmic reticulum (SR) — not from extracellular fluid.

Which protein does Ca²⁺ bind to initiate contraction?

Troponin C (TnC) on the thin filament.

What happens when Ca²⁺ binds TnC?

TnI moves away, exposing myosin-binding sites on actin.

What protein actively pumps Ca²⁺ back into the SR?

SERCA pump (Ca²⁺-activated ATPase)

What protein binds Ca²⁺ inside the SR to lower free Ca²⁺ levels?

Calsequestrin

What stops contraction and causes relaxation?

Return of cytoplasmic Ca²⁺ to low levels → TnI rebinds to actin, blocking myosin.

By what are muscle fibers innervated ?

By motor neurons that originate in the spinal cord or brainstem

• the axons of the neurons branch as they near the muscle giving rise to twigs or terminal branches that end on individual muscle fibers

What happens at the neuromuscular junction

The myelin sheath of the axon ends and the terminal portion of the axon is covered by only a thin portion of the neurilemmal cells (Schwann cells) with its external lamina

What are intercalated discs ?

They are the attachment site between cardiac muscle cells, they appear in the LM as a densely staining linear structures that is oriented transversely to the muscle fibers

• consist of short segments arranged in a step like fashion

• in the TEM we find transverse componetn’s that cross the fibers at a right angle to the myofibrils

What are the lateral components

Components hat occupies a series of surfaces perpendicular to the transverse compartment and lie parallel to the myofibrils

What neurotransmitter is released at the neuromuscular junction?

Acetylcholine (ACh)

What receptor does ACh bind to on the sarcolemma?

Nicotinic ACh receptor (Na⁺ channel)

What enzyme breaks down ACh in the synaptic cleft?

Acetylcholinesterase

What happens when ACh binds its receptor?

Na⁺ influx → depolarization of the muscle cell

What cells enable skeletal muscle regeneration?

Satellite cells

Which transcription factor defines satellite cells?

Pax7

What proprioceptor senses muscle stretch?

Muscle spindle

Where are T-tubules located in cardiac muscle?

At the Z-line (unlike skeletal muscle, where they're at the A–I junction)

What type of ryanodine receptor is found in cardiac muscle?

RyR2 — the cardiac isoform, activated by calcium-induced calcium release

What triggers RyR2 to release Ca²⁺ in cardiac muscle?

Ca²⁺ influx through L-type Ca²⁺ channels (DHPRs) in the T-tubule membrane

What cells are responsible for conduction of impulses in the heart?

Purkinje fibers

What’s different about calcium handling in cardiac vs skeletal muscle?

Cardiac contraction requires extracellular Ca²⁺ influx; skeletal does not.

Why is there a delay in cardiac muscle twitch contraction?

Due to the slow opening of DHPR Ca²⁺ channels and calcium-induced calcium release

Which ATPase helps remove Ca²⁺ from the sarcoplasm post-contraction?

SERCA (Ca²⁺-ATPase of the SR)

What regulatory molecule replaces troponin in smooth muscle?

Calmodulin

What enzyme activates smooth muscle contraction?

Myosin Light Chain Kinase (MLCK)

What activates MLCK?

Ca²⁺–calmodulin complex

What two proteins bind actin and inhibit contraction until Ca²⁺ levels rise?

Caldesmon and Calponin

What structural protein anchors actin filaments in dense bodies?

α-Actinin

What intermediate filaments help anchor dense bodies?

Desmin and Vimentin

What is the structural analog of Z-lines in smooth muscle?

Dense bodies

What type of filament arrangement is found in smooth muscle thick filaments?

Side-polar (not bipolar as in skeletal)

What happens when the regulatory light chain of myosin is phosphorylated?

Myosin can bind actin → cross-bridge cycle begins

What helps reduce the inhibition of myosin-binding sites on actin?

Phosphorylation of caldesmon (and possibly calponin)

What is the primary Ca²⁺-dependent regulator of contraction in smooth muscle?

Calmodulin (binds Ca²⁺ and activates MLCK)

What enzyme phosphorylates the regulatory light chains of myosin?

Myosin Light Chain Kinase (MLCK)

What triggers Ca²⁺ release from the smooth muscle sER?

IP₃ binds to IP₃ receptors on sER

What is the latch state in smooth muscle?

A low-energy, sustained contraction state where dephosphorylated myosin stays bound to actin

How do neurotransmitters reach smooth muscle cells?

Through diffusion from boutons en passant, not direct synaptic clefts

What structure enables coordinated contraction between smooth muscle cells?

Gap junctions (nexus)

Which second messenger mediates relaxation via NO in smooth muscle?

cGMP, activated by guanylate cyclase

What transcription factor regulates smooth muscle differentiation?

Serum Response Factor (SRF)

What connective tissue proteins do smooth muscle cells synthesize?

Type III collagen, type IV collagen, elastin, proteoglycans

What types of cells can differentiate into smooth muscle?

Mesenchymal stem cells, pericytes, myoepithelial cells, fibroblasts