Muscle tissue

Muscle fibers Rich capillary network Fibrous connective support tissue

Donley et al., 2004

Muscle types

Skeletal muscle40% of body massMultinucleate cells –very long!Muscle has cross-striations

Voluntary (higher brain) controlContracts rapidlyTerminal cell type

Cardiac muscle

Cross-striations Intercalated discs- intercellular

communication Involuntary contraction-speed and strength

regulated by endocrine and nervous systems

Myogenic contraction

Smooth muscle

Non-striated Individual cells Visceral smooth muscle- forms sheets Slow contracting Involuntary contraction

2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter

Muscle tissue nomenclature

Cytoplasm = sarcoplasm ER = sarcoplasmic reticulum Cell membrane = sarcolemma

Skeletal muscle

Muscle cells fuse together during development (up to 30 cm long)

Nuclei are usually peripheral

2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter

Muscle sheath

EpimysiumDense connective tissue that surrounds entire

muscle Perimysium

Thin connective tissue layer that surrounds fiber bundles

EndomysiumSurrounds each muscle fiber (cell)Mainly reticular fibers and basal lamina

Architecture of a skeletal muscle fiber Muscle fibers are composed of myofibrils Myofibrils are composed of repeating units called

sarcomeres Sarcomeres are the smallest functional unit of

skeletal muscle Sarcomeres are composed of overlapping thick and

thin filaments Thin filaments are composed of actin and associated

proteins Thick filaments are composed of myosin

Thick filaments-Myosin II

Thin filaments- Actin and associated proteins

M line-Creatine kinase

Sarcomere regions

I Band, isotropic- similar polarization characteristics throughout

A Band, anisotropic- different polarization characteristics throughout

H Band- ‘heller’ or bright Z line, ‘Zwischenscheibe’ or between M line, ‘mittel’ or middle

Insect flight muscle

2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter

Figure 10—10. Electron micrograph of skeletal muscle of a tadpole. Note the sarcomere with its A, I, and H bands and Z line.

Sliding filament theory of muscle contraction

© 2000 by W. H. Freeman and Company

Molecular characteristics of contractile filaments Myosin II Each thick filament contains more than

200 myosin molecules

Myosin head ATPase activity Actin binding Molecular hinge

Actin thin filament 2 strands of F actin formed from globular or G

actin Tropomyosin- double stranded long filament

that wraps around F actin Troponin

TnI- inhibits myosin-actin interactionTnT- binds to tropomyosinTnC- binds to calcium

See it now!!!!

Troponin

Troponin•T, tropomyosin binding site•C, calcium binding site•I, inhibitory site

Mechanism of contraction1. Calcium binds to TnC2. Conformational change in troponin exposes

myosin binding site on actin3. Myosin binds to actin4. ATP cleavage causes myosin to bend5. This causes actin filament to move pass

myosin6. A new ATP binds to myosin head. This causes

head to de-attach and swing back on hinge

Thick and thin filaments

Actin (alpha helix) – thin filament

Myosin – thick filament

Z-disc

Thick and thin filaments

Excitation contraction coupling

Depolarization of sarcolemma causes release of calcium within muscle fiber

Application of electrical stimulus to area of I band produces sarcomere shortening

How do changes in membrane potential translate into an increase in intracellular calcium?

T-tubules

Invaginations of sarcolemma that surround myofibril at every sarcomere in the region of the A-I band

Adjacent to each T-tubule is a sarcoplasmic reticulum, which stores calcium

T-tubules

Action potential travels along sarcolemma, down T-tubule

This causes calcium to be released from sarcoplasmic reticulum

T-tubules in fish muscle

Long live the Triad!!!- SR, T-tubule, SR

The triad

the triad is a diagnostic feature of skeletal muscle

It is composed of two lateral cisternae on either side of a T-tubule.

It is not found in cardiac or smooth muscle

Neuromuscular junction

© 2000 by W. H. Freeman and Company.

Lodish et al., © 2000 by W. H. Freeman and Company, [Adapted from M. J. Berridge, 1993, Nature 361:315.]

Calcium channel inhibitors- ryanodine blocker

AmlodipineNorvasc

Skeletal Muscle Innervation

One muscle fiber innervated by one motor axon

Motor unit- motor axon and the muscle fibers that it innervates

Graded contraction depends upon # motor units recruited

Modulators of the neuromuscular synapse Strychnine- antagonist at the glycine

inhibitory synapse (activation of glycine receptors inhibits neurons by opening Cl- channels).

Nicotine – derive from the dried leaves of the tobacco plant Nicotinia tabacum

Muscarine -from the poisonous red mushroom Amanita muscaria

Physostigmine-inhibits Ach-esterase at neuromuscular junction

Calabar bean (Physostigma venenosum)

Acetylcholinesterase inhibitors

Organophosphate insecticides such as parathion and malathion

Organophosphate nerve gases such as sarin.

Acetylcholinesterase inhibitors

Organophosphate pesticides and physostigmine inhibit Ach-esterase by forming a covalent bond in the Ach binding pocket of the enzyme

Much slower dissociation from enzyme than Ach, which binds for 30-40 s. Physostigmine and organophosphates may remain bound to enzyme for 30-40 min or much longer.

Toxins from Clostridium bacteria that affect presynaptic motor terminals:•Tetanus toxin•Botulinum toxin cleave the vesicle SNARE protein,

synaptobrevin

Tetanus toxin

Poisoning with the tetanus toxin from Clostridium tetani bacteria inhibits the secretion of inhibitory neurotransmitters (GABA, glycine) controlling motor neurons in ventral spinal cord.

This produces a disinhibition of skeletal motor neurons, leading to overexcitement and hypercontraction of skeletal muscle fibers.

Botulinum toxin

Inhibits synaptobrevin in ACh neurons innervating skeletal muscle, preventing ACh release.

Cardiac muscle

Striated, one or two nuclei per cell Nucleus located in the center of cell Intercalated discs

Zonula adherens Desmosomes Gap junctions

40% of cytoplasm is mitochondria (compared to 10% in skeletal muscle).

Figure 10—27. Electron micrograph of a longitudinal section of heart muscle. Note the striation pattern and the alternation of myofibrils and mitochondria rich in cristae. Note the sarcoplasmic reticulum (SR), which is the specialized calcium-storing smooth endoplasmic reticulum. x30,000.

Figure 10—22. Drawing of a section of heart muscle, showing central nuclei, cross-striation, and intercalated disks.

Figure 10—23. Photomicrograph of cardiac muscle. Note the cross-striation and the intercalated disks (arrowheads). Pararosaniline—toluidine blue (PT) stain. High magnification.

Figure 10—24. Longitudinal section of portions of 2 cardiac muscle cells. The transversely oriented parts of the intercalated disk consist of a fascia adherens and numerous desmosomes. The longitudinal parts (arrows) contain gap junctions.

Figure 16-75. Effect on the heart of a subtle mutation in cardiac myosin. Left, normal heart from a 6-day old mouse pup. Right, heart from a pup with a point mutation in both copies of its cardiac myosin gene, changing Arg 403 to Gln. Both atria are greatly enlarged (hypertrophic), and the mice die within a few weeks of birth. (From D. Fatkin et al., J. Clin. Invest. 103:147, 1999.)

2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter

Smooth muscle

Found in visceral organs, arteries and veins, iris of the eye

Each cell is surrounded by reticular fibers and a basal lamina

These harnesses help to convey force started by smooth muscle contraction

Smooth muscle

No T-tubules, SR is poorly developed Actin and myosin are no organized into

lattice network. Excitation-contraction coupling-

Calcium binds to calmodulinCauses phosphorylation of myosin light chain

kinaseNo tropomyosin

© 2000 by Geoffrey M. Cooper

Contraction in smooth muscle is controlled by phosphorylation of myosin

Figure 10—29. Photomicrographs of smooth muscle cells in cross section (upper) and in longitudinal section (lower). Note the centrally located nuclei. In many cells the nuclei were not included in the section. PT stain. Medium magnification.

Figure 10—30. Drawing of a segment of smooth muscle. All cells are surrounded by a net of reticular fibers. In cross section, these cells show various diameters.

Figure 10—33. Smooth muscle cells relaxed and contracted. Cytoplasmic filaments insert on dense bodies located in the cell membrane and deep in the cytoplasm. Contraction of these filaments decreases the size of the cell and promotes the contraction of the whole muscle. During the contraction the cell nucleus is deformed.

Smooth muscle lacks troponin but has tropomyosin. Another protein, Caldesmon, has been implicated in smooth muscle contraction.•Low Ca2+ - caldsemon binds to actin-TM and prevents myosin from binding•High Ca2+ - Ca2+-CaM complex binds to caldesmon, releasing it from actin