Topic 1:Intro to Muscles Motility & Force Generation

• 1. Striated (skeletal + cardiac)
• 2. Smooth

highly organized into sarcomere structures giving a “striated” appearance under the microscope

performs mechanical work via the skeleton under voluntary neural control

performs mech work in the heart under its own pacing control modulated by ANS

contractile apparatus is loosely organized without a defined banding pattern

performs mechanical work in many target organ systems and is modulated by NT's, metabolic, local and hormonal factors.

1. Cells are multinucleated, striated and organized in parallel bundles

• 2. Diameters-->10 mm - 100 mm
•    lengths --> 1 mm - 20 cm

• 3. Activated by motor neurons from CNS
• (spinal cord) at neuromuscular junctions leading to muscle action potentials and
• voluntary contraction

1. no attachments to a skeleton which limit movement

• 2.cells are much smaller and attached (physically & electrically) to each
• other via Gap Junctions.

3.spindle shaped mono-nucleated cells w/ short lengths of  50 – 400 μm and diameters of 2 – 10 µm

4.found in a wide variety of organ systems

1. cells aka "myocytes" 

2. diameter: 25 mm; length: 150 mm

3. 2 nuclei

4. myocytes are striated.

5. organized in layers/"syncytium"

6. connected by intercalated discs with gap junctions.

7. Myocytes are not individually innervated, but regions innervated by neurons from ANS.

8.Mechanical activity is rhythmical paced SA node of the right atrium (modulated by NT)

muscle > myofiber > myofibril

• - has a "field" structure
• - formed from a syncytium of cells, not from distinct fibers.

• 1. Collagen Matrix
• 2. Dystroglycan Complex (Dystrophin)

• - surrounds entire muscle fibers
• - collagen laid down by fibroblasts

- protein complex that helps w/ membrane stability of muscles

- lack of dystrophin leads to Muscular Dystrophy

- basic repeating contractile units in striated muscle

- present in skeletal and cardiac

- A band = dark = thick filament = whole length of myosin superimposed by actin

- I band = light = thin filament = actin only

- H zone = region of myosin only

1. Alpha-actinin: interacts w/ thin filaments @ Z line

2. Titin filament: runs for M line to Z line and tethers both the thin and thick filament together (keeps sarcomere in line)

Skeletal: organized into large fibers to form whole muscles

Cardiac: organized into “syncytial field” structure of individual myocytes

I band and H zone SHORTENS

A band remains the SAME

the basis of striated muscle force generation and shortening

Myosin

- Each thick filament contains hundreds of myosin molecules which contain:

• 1. S1 region
• 2. S2 region
• 3. Light Chains (ELC + RLC)

• - business end of the mysosin molecule
• - regions that binds to the actin
• - contains ATP pocket (myosin is an ATPase)
• 
  

• - "rope" part of the myosin
• - has a swivel that allows it to stick out
• - springy elastic protein

• (1) ELC 
• (2) RLC = regulatory light chain

• - Hydrolysis of ATP
• - This is CHEMOMECHANICAL TRANSDUCTION

- double head arrangement increases the probability of actomyosin binding and cycling via cooperativity

- angles at which the crossbridges stick out of the thick filament do not  line up w/ each thin filament

• - double heads improve likelihood of alignment and increase contractile
• efficiency.

• •Both
• heads are otherwise independent force generators.

• Start: "energized crossbridge" = ADP + Pi bound to myosin head
• 1. Crossbridge binds to actin
•      - due to rise in [Ca++]
• 2. Crossbridge moves/bound more tightly
•     - due to release of ADP + Pi
• 3. Crossbridge detaches
•     - due to ATP binding to myosin
• 4. Energize Crossbridge
•     - due to hydrolysis of ATP to ADP

YES!

S1 Head conformational change.

Between the head region and the light chains of myosin

For Myosin II (striated &smooth muscle) molecular motor can generate up to 10 pN with a stroke in the 5-10 nm/CB cycle range

There are 17 Families & ~140 Distinct Motor Proteins

Myosin II is only a small portion of motor proteins

Ca++. Released by sarcoplasmic reticulum under the control of electrical stimulation via action potentials

troponin and tropomyosin.

regulate the crossbridge cycle by covering and uncovering myosin binding site on actin depending upon [Ca++]



Tropomyosin = rope-like (covers up myosin crossbridge binding site on actin)

Troponin = physically binds with Ca++

- consists of 3 sub-units.

1. Troponin T (TnT) binds tropomyosin @ every 7 actin molecules

2. Troponin I (TnI) physically inhibits binding of myosin to actin when no Ca++ is present.

3. Troponin C (TnC) binds Ca++.

the conformation changes moving TnI off the myosin binding site on actin permitting crossbridge cycling

There are 4 Ca2+ binding sites on TnC: 2 are always filled by Mg2+ and the other 2 can bind Ca2+

• cardiac: One of the two Ca2+ binding sites
• on cardiac troponin is not functional

therefore, it only takes 1 Ca++ ion to activate whole system for cardiac. Skeletal requires binding of 2 Ca++

Excitation Contraction Coupling

• EC coupling is the sequence of events that link the depolarization of the surface membrane with tension development by the
• contractile machinery

the propagation of an action potential along the sarcolemma

No! They also have no direct CNS input

ANS

Calcium is released from SR like in skeletal muscle, but it also directly enters the cell from the outside via calcium channels.

compared to nerve or skeletal muscle, cardiac muscle has a much longer action potential duration due to the Ca2+ conductance.

• 1. depol of plasma membrane
• 2. opening of voltage-gated Ca++ channels in T-tubules
• 3. influx of Ca++ in cytosol
• 4. Ca++ binds to Ca++ receptors on SR
• 5. more influx of Ca++ in cytosol
• 6. increase cytosolic [Ca++] --> contraction

• In humans and large mammals,
• 70% of the Ca++ comes from the SR
• 30% from the outside

Ca++ must be proportionally pumped back to both reservoir sources for relaxation to occur

• 1. SR Ca2+ pump
• - resequesteres intracellular Ca2+ from
• the SR
• - rate of resequestration is modulated by phospholamban (PLB)
• - process uses ATP

• 2. Sodium-Calcium Exchanger
• - extrudes extracellular portion of Ca2+
• - 3Na/1Ca, no ATP used

• 3. T-Tubule Ca-pump
• - extrudes extracellular portion of Ca2+

- mediate the release of calcium ions from the sarcoplasmic reticulum

- releases calcium upon calcium binding

Allosteric Regulation (cooperative)

the sources of calcium necessary to initiatecontraction.