ANNOUNCEMENTS Review Session this Friday: 12:20 Morrill 349 IMAGE523 Poster Team: Let’s Meet After Class Write Abstract Poster Design Discussion: Exam,

ANNOUNCEMENTS

Review Session this Friday: 12:20 Morrill 349

IMAGE523 Poster Team: Let’s Meet After Class

Write AbstractPoster Design

Discussion: Exam, Midsemester Review

Needs Improvement

Pace of class meeting (12)

More explanation/detail on ppt slides (5)

Lab/Lecture Linkage (4)

More dental coverage (2)

Many other thoughtful ideas (1)•limit reading•more previous exams•figures in lab guide•lab more hands-on•more graded assignments

•and others

Structure - FunctionMuscle Contraction

Striated NonstriatedSkeletal SmoothCardiac

Striated Muscle: Sarcomere

Striated Muscle: Sarcomere- Z line to Z line Z lineZ line

SarcomereZ line to Z line

A bandI bandM lineH band

Thin filaments– Microfilaments (Actin)– Anchored to Z line by -actinin, nebulin– Associated with Troponin, Tropomyosin,

TropomodulinThick filaments

- Myosin: 2 Heavy / 4 light chains- Anchored to Z line by Titin- M line anchors: myomesin and C-proteins

Molecular Components of Sarcomere

This is an electron micrograph of a section through a sarcomere of a skeletal muscle fiber.

Where in the sarcomere is the section taken?

Striated Muscle Contraction

Thin FilamentTropomyosin: – winds around actin – obscures actin-myosin binding site

Troponin Complex – Troponin T: interacts with Tropomyosin – Troponin I: prevents myosin-actin binding – Troponin C: binds Ca++, allowing myosin-actin binding

Striated Muscle Contraction

Thin FilamentTropomyosin Troponin – Troponin T – Troponin I – Troponin C

Ca+2

Contraction of Striated Muscle

- Release of Calcium from Sarcoplasmic Reticulum

- Calcium binds to Troponin

- Tropomyosin/Troponin shift to expose binding site

- Myosin head binds to Actin; Pi released

- Release of ADP from Myosin ---> POWERSTROKE

- Binding of ATP: Myosin detaches from Actin

- Splitting of ATP---> ADP + PI; Myosin head is reset

QuickTime™ and aAnimation decompressor

are needed to see this picture.

http://www.sci.sdsu.edu/movies/actin_myosin.html

Excitation-Contraction Coupling

• T tubules• Sarcoplasmic reticulum: Calcium• Triads

Sarcoplasmic Reticulum and T-tubules

T-tubules

SarcoplasmicReticulum

Triad

Striated Muscle Structure

• T tubules• Sarcoplasmic reticulum: Calcium• Triads: juncture of T-tubules & SR

- Must release calcium from sarcoplasmic reticulum to initiate the contraction process.

Excitation-Contraction Coupling

Muscle Action Potential

Transverse Tubules

Sarcoplasmic Reticulum

Calcium release

Excitation-Contraction Coupling

Muscle Action Potential

Transverse Tubules

Sarcoplasmic Reticulum

Calcium release

T-tubule membrane

Smooth Muscle Contraction

- No organized sarcomere structure

- Actin filaments are associated with tropomyosin but

Not Troponin

What controls actin-myosin interaction?

Smooth Muscle Contraction

-Myosin interacts with actin only when the myosin light chains are phosphorylated

Smooth Muscle Excitation-Contraction1) Excitation=> Ca++ influx

2) Ca++ binds Calmodulin

3) Ca++-Calmodulinactivates myosin light chain kinase (MLCK )

4) MLCK phosphorylates myosin light chains

5) Myosin binds actin => contraction

Regulation of Smooth Muscle Contraction

Nonneural regulation

Hormonal: Oxytocin- uterine contraction

Nitric Oxide (NO):

Produced by endothelial cells of

arterioles

Relaxes smooth muscle

Mice have been produced whose eNOS (endothelial cell NO synthase) genes been "knocked out”. Predict the blood pressure levels of these mice.

Nitric Oxide ----> increased [cGMP]

activates a kinase

inhibits Ca++ influx into smooth muscle cell

decreased calcium-calmodulin stimulation of

MLCK

decreased phosphorylation of myosin light

chains decreased smooth muscle tension

development

vasodilation (expansion of vessel lumen)

Nitric Oxide ----> increased [cGMP]

activates a kinase

inhibits Ca++ influx into smooth muscle cell

decreased calcium-calmodulin stimulation of

MLCK

decreased phosphorylation of myosin light

chains decreased smooth muscle tension

development

vasodilation (expansion of vessel lumen)

What would be the effect of drugs that inhibit the breakdown of cGMP ?

Drugs that inhibit the breakdown of cGMP potentiate (increase) the effects of

NO actions on target cells.

EXAMPLE: Viagra and other inhibitors of cGMP-dependent phosphodiesterase

Innervation of Muscle

Smooth Muscle

Innervation: boutons en passant acetylcholine

Stimulation spread by gap junctions

Innervation of Smooth Muscle

A multiunit system: fine innervation for regulation of individual cells; cells that control the iris opening

A single unit system:1 neuromuscularJunction serves asheet of muscle fibers; stimulus transmitted to otherMuscle cells via gapjunctions; wall of intestine

Innervation of Striated Muscles

Skeletal Muscle: each muscle fiber has at least 1 neuromuscular

junction

Cardiac Muscle: contract spontaneously

rate governed by innervation

excitation spread by gap

junctions

Motor Neuron

Nerve Action Potential

Synapse

Neuromuscular Junction

Neurotransmitter (ACh)

Receptors (AChR)

Muscle Action Potential

Transverse Tubules

Sarcoplasmic Reticulum

Calcium release

Neuromuscular Junction• Nerve stimulation

• Action potential

• Opening of calcium channels

• Exocytosis of synaptic vesicles

• Acetylcholine release

• Binding to Acetylcholine receptors

(AChR)

• Muscle depolarization including T-

tubules

• Opening of Calcium channels in SR

Motor endplate=Neuromuscular Junction

• Synaptic vesicles

• Active zones

• Junctional folds

• AChR (acetylcholine receptor)

clusters

• Schwann cell

Junctional Folds

Types of skeletal muscles

Fast muscles– Strong and rapid contraction; rapid fatigue– ATP from anaerobic glycolysis– Phasic motor neuron

Slow muscles– Slower but sustained contraction– ATP from oxidative respiration (mitochondria)– Tonic motor neuron

http://www.lionden.com/muscle_animations.htm

Stain for ATPase activity: dark-->faster contracting

Synaptic input influences

properties of muscle fibers

Calcineurin

Activates NFAT (nuclear factor of activated T cells)

Transcription of slow muscle program