FOUR BASIC STEPS OF MUSCLE CONTRACTION CYCLES

1.attach. of cross-bridge to thin filament

2.movement of X-bridge => prod. tension in the thin filament

3.detach. of the X-bridge fr. thin filament

4.Energizinng the cross bridge so it can again attach to a thin filament & repeat the cycle

POWER STROKE

-ATP hydrolysis puts myosin in a high energy "cocked" state (like a streatch skin)

-Binding of myosin -> actin releases energy

-release = conformational change in myosin = "the power stroke"

-result = actin is pulled toward center of sarcomere

-Binding of myosin --> actin needs ATP --> ADP to "energize"

-Movement of myosin attach. to actin

-detach. of myosin fr. actin (needs ATP Binding)

-repeat

• smooth mus that do use action potential open voltage-gated Ca2+ chann.
• some smooth muscles spontaneously generate action potentials

- AP triggers the DHP receptor (voltage-sensitive)

- DHP bound to raynodine receptors

-ryanodine receptor channel opens Ca2+

-no motor end plate

- Can depolarization/hyperpolarization

- swollen regions in autonomic neurons varucosites realse neurontransmitter

- Smooth Mus. can slao respond to hormones

• shares similarities to both smooth and skele muscle
• involuntary like smooth
• striated like skele
• has troponin, tropomyo, sarcomeres: actin and myo
• Join end to end in intercalated disks
  • joined by desosomes
  • has many gap junct.

+= amt. of SR present in MUS type

-made of bundles of myosin motors

-is actually apolymer of myosin molecules, each of which has a flexible cross-bridge that binds ATP and actin

-

CROSS BRIDGE CYCLE

(X-bridge)

1.The myosin-bind. site on actin = avail. so the energize cross-bridge binds

2.The full hydrolysis and departure of ADP + Pi causes the flexing of the bound cross bridge

3. Binding of a "new" ATP to the X-bridge uncouples the bridge

4. Hydrolysis= the bound ATP energizes or "re-cocks" the bridge

• trigger is inc. Ca2+ concin.
• Troponin binds to Ca2+ = changes shapes = in tropomyo moving = allows myo to bind
• cross-bridge cycle

Ca2+ IONS

PT. 2

- Regulates myo-actin cycle (X-bridge)

- Levels of Ca2+ det. if myo can bind to actin

- 2 proteins= troponin + tropomyosin = help regulate process

- LOW Ca2+: tropomyo. covers binding sites on actin = prevents myo binding = troponin hods tropomyo in place

- HIGH Ca2+: Ca2+ binding on troponin = relaxes binding to tropomyo = tropomyo moves & uncovers binding sites on actin

• Muscle induced EPP is usually much larger than an EPSP

       One EPP results in action potential

• No IPSPs

• Eye and finger muscles have small motor units
• Leg and arms have bigger motor units

• Slow fibers (type I) have lower ATPase activity
• Fast fibers (type II) have lower ATPase activity

• Oxidative fibers use primarily oxidative phosphorylation: have high numbers of mitochondria, surrounded by many blood vessels, have red color
• Glycolytic fibers use primarily glycolysis: few motochondria, large stores of glycogen, few blood vessels, white color

• Mech. shares features of both smooth and skele
• Action potential results in depolarization
• on T-tube, voltage-gated Ca2+ chann. open (L-type Ca2+ chann)
• Leads to greater rel. of Ca2+ fr. sarcoplas. reticulum

1. Hydrolysis of ATP by myosin energizes the X-bridges, providing energy for force gen.

2. binding ATP to myo = dissassociates x-bridges bound to actin = allows bridges to repeat cycle of activity

3. hydrolysis of ATP by the Ca2+ -ATPase in the Sacroplas. reticul. provides energy for the active trans. of  Ca ions into the reticu. = lowers cystolic Ca to prerelease levels = ends the contraction = the mus. fiber can relax

- action potential (AC) is initiated in mus. mem.

- delay b/t AP and contract

- delay due to time need to release Ca2+

HOW NEUROMUSCULAR JUNCTION WORKS

PT 1

1. synaptic cesicle fusion (triggered by Ca2+) in motorneurons releases acetlcholine

2. on the membrane of the mus. fiber, acetylcholine receptors respond to acetylcholine binding by inc. Na+ entry into the fiber, causing a graded depolarization.

3. the graded depolariz. typically exceeds threshold for the nearby voltage-gate Na+ and K+ channels = so an action potential occurs on the mus. fiber

1. spontaneous elect. activity in the plasma mem. of the mus. fiber

2. neurotansmitters released by autonomic neurons

3. Hormones

4. Locally induced changes in the chem composition (pancrine agents, acidity, oxygen, osmolarity, and ion concin.) of extracell. fluid surrounding the fiber

5. strech

• Load = force exerted on muscle by an object (weight on bones)
• Tension = force exerted by the muscle on an object
  

• Ryanodine receptor channels become leaky to Ca²⁺, leads to preteases breaking down myosin
• Leads to soreness until new protines are made
• Depletion of Energy stores such as Muscle glycogen
  

• Maximal tetanus is usually about 3-5 times greater than maximal isometric tension
• Maximal tetanus results is persistent intracellular Ca²⁺
• During isometric tension (tension from 1 action potential), intracellular Ca²⁺ falls quickly
  

MEMBRANE POTENTIAL

SKELE MUS & CARDIAC CONTRACTIONS

[image]

cardiac contac are prolonged

MEMBRANE POTENTIAL

SKELE MUS & CARDIAC CONTRACTIONS

[image]

cardiac contac are prolonged

- rhythmic changes in the membrane potential of smooth mus. results in rhythmic patterns of action potentials and therefore rhythmic contraction in the gut neighboring cells use gap junction to further coordinate these rhytmic contractions

[image]

-A  single motor unit consists of a motor neurons and all of the mus. fibers it contols.

-A  single motor unit consists of a motor neurons and all of the mus. fibers it contols.

• A motor unit is composed of muscle fibers of the same type
• Muscles have al thress types in different portions

• Smaller neurons tend to be activated first
• Smaller motorneurons tend too innervate slow-oxidative fibers
• Medium size motorneurons tend to innervate fast-oxidative
• Large motorneurons innervate fast-glycolytic

• Fast twitch: a fast 10 msecs
• Slow twitch: around 100 msecs
  

-has opposite effect of muscle distrophy

- edurance training: inc. mitochondrea numbers, blood vessles around mus., and resistance to fatigue

- high intensity: (str./aerobic) training stimulates inc. in fiber diameter, glycolytic enzyme levels

- also inc. and more efficent neural control

-Destroy the motorneuron and the innervated mus. w/ atophy (shrink in diameter & exert less force)

-Lack of use will cause same effect

• Existing pool of ATP can only support a few twitches
• Need to make more ATP rapidly

-regulates with cross-bridge cycle occurs

-takes the place of troponin

- 1 motor neuron may innervate many mus. fibers (cells)

- this is called a motor unit

- the smaller the unit = finer the control

- Mus fiber membrane is in folds

- motor neurons typically release acetylCholine

- where the motor neurons synapses with the mus.

- AP in the motor neuron cause acetylcholine release into the neuromuscular juntion

- Muscle contraction follows the delivery of acetylcholine to the muscle fiber

- uses myo light chain kinase instead of troponin, use but don't need action potentials

- Lower rate of cross-bridge cycling and longer twitch duration

- myo light chain phophatase turns off cross-bridge cycle

- can sustain contraction (latch state)

- Innervated by autonomic nervous system

-excitation-contraction coupling,

   -->in all 3 mus. types, Ca2+ is the trigger

- signaling triggers excitatory postsynaptic potential which leads to an AC

   --> in mus. its called end-plate potential EEP

-action potential floes into t-tubes

- dihydropyride (DHP) receptor acts as a voltage sensor

- Ryanodyne receptor changes conformation

- ranyodynr receptor is an ion channel = opens

• No tetanus (prolonged contraction)
• Refactory period
• Increased entry of Ca2+ = mediated by norpinephrine
• Specialzed pacemaker cells sets up cardiac rhythm
• depolarization spreads via gap channels
• there always will be a relaxation after contraction
  • PM= Consistent patterns
  • DP= spreads via gap channels

• At cellular level
  • Increase in frequency of stimulation to single muscle fibers leads to summation and tetany
• At the systems level
  • Increased recruitment of motor units

-At the cellular level:
   -->Increase in frequency of stimulationto a single mus. fibers leads to summation and tetany

- at the systems level:

    -->Increase recruitment of motor units

    -->small --> medium --> large motor units

RELAXED & CONTRACTED

DIAGRAM

[image]

RELAXED & CONTRACTED

-Think myo based & thin actin based filaments biochem similar to those in skele. mus. fibers.

  --> Interact to cause smooth mus. contract.

RELAXED & CONTRACTED

DIAGRAM

[image]

RIGORMORTIS

PT. 2

-dead = no ATP made

-No ATP on myo = high affinity for actin

-stiff mus. for ~40hrs. after death

SARCOPLASMIC RETICULUM

(SR)

- equivalent of endoplasmic reticulum

- lateral sacs contain stores of Ca2+

- transverse tubes are associated w/ lateral sacs

1. resting state = low cytoplasmic Ca2+

   -->tropomyo blocks myo binding sites in actin

2. excitatory action potential triggered in mus. mem.

3. Ca2+ stores in sarcoplas. reticulum are realeased into cytoplasm

4. Ca2+ binds to troponin -> tropomyo uncovers binding sites -> myosin binds and pulls (X-bridge cycle)

SEQUESNCE OF EVENTS B/T MOTOR NEURON AP AND SKELE MUS. FOBER CONTRACT.

PT. 1

1. action  potential is initiated and propogates to motor neuron axon terminals

2. Ca enters axon terminals through voltage-gated Ca channels.

3. Ca entry triggers release of ACh from axon terminals

4. ACh diffuses fr. axon terminals to motor end plate in muscle fiber.

5. ACh binds to nicotonic receptors in motor end plate, increasing their permiability to Na⁺ and K⁺.

6. More Na⁺ moves into the fiber at the motor end plate than K⁺ moves out, depolarizing the membrane, producing the end plate potential (EPP).

SEQUESNCE OF EVENTS B/T MOTOR NEURON AP AND SKELE MUS. FOBER CONTRACT.

PT. 2

7. Local currents depolarize the adjacent muscle cell plasma membrane to its threshold potential, generating an action potential that propagates over the muscle fiber surface and into the fiber along the T-tubules.

8. Action potential in T-tubules triggers release of Ca²⁺ from lateral sacs of sacroplasmic reticulum.

9. Ca²⁺ binds to troponin on the thin filaments, causing tropomyosin to move away from its blocking  position, thereby uncovering cross-bridge binding sites on actin.

10. Energized myosin cross-bridges on the thick filaments bind to actin:

                                                         A + M x ADP x P₂ -------> A x M x ADP x P₂

SEQUESNCE OF EVENTS B/T MOTOR NEURON AP AND SKELE MUS. FOBER CONTRACT.

PT. 3

11. Cross-bridge binding triggers release of ATP hydrolysis products from myosin, producing an angular movement of each cross-bridge:

                                 A x M x ADP x P₂ --------> A x M + ADP + P₂

12. ATP binds to myosin, breaking linkage between actin and myosin and thereby allowing cross-bridges to dissociate from actin:

                                      A x M + ATP --------> A + M x ATP

13. ATP bound to myosin is split, energizing the myosin cross-bridge:

M x ATP --------> M x ADP x P₂

SEQUESNCE OF EVENTS B/T MOTOR NEURON AP AND SKELE MUS. FOBER CONTRACT.

PT. 4

14. Cross-bridges repeat steps 10 to 13, producing movement (sliding) of thin filaments past thick filaments. Cycles of cross-bridge movement continue as laong as Ca²⁺ remains bound to troponin.

15. Cytosolic Ca²⁺ concentration decreases as Ca²⁺ is actively transported into sarcoplasmic reticulum by Ca²⁺ - ATPase.

16. Removal of Ca²⁺ from troponin restores blocking action of tropomyosin, the cross-bridge cycle ceases, ant the muscle fiber relaxes.

• Conductive failure as a result of increased extracellular [K⁺] after Aps. No Ap propagation.
• Lactic acid buildup affects Ca²⁺ release
• Inhibition of crossbridge recycling as a result of buildup of ADP an Pi delays crossbridge detachment.
  

• Slow-oxidative
• Fast oxidative
• Fast-glycolytic

- Skele Mus.: Inc. cytosolitic Ca2+ --> Ca2+ binds to troponin on thin filaments--> Conformational change in toponin moves tropomyo out of blocking position --> Myo cross-bridge bind to actin --> cross-bridge cycle

- Smooth Mus.: Inc. cytosolitic Ca2+ --> Ca2+ binds to calmodulin in cytosol --> Ca2+ calmodulin complex binds to myo light-chain kinase --> Myo light-chain kinase uses ATP to phoyophoytate myo cross-bridges --> Phosphorylated cross-bridges bind to actin filaments --> cross-bridge cycle prod. tension & shortening

SMOOTH & SKELE MUS CONTRACT

PT. 2

- Ca ions play as major regulator roles in contrac. of both smooth and skele. mus., but the Ca in smooth mus. bind calmodulin activates myo light chain kinase

• Paracrine signaling (ex: nitric oxide)
• Acidity
• oxygen and CO2 concin
• Ion concin

• SINGLE-UNIT: conn. by gap junct., undergo synchronous contract.
• Multi-unit: few gap junct. contract indep. respond to neurotrans, and hormones, but don't often make action potential

1. excitation (depolar. of plasma mem.)
2. opening of plas mem. L-type Ca2+ chann in t-tubes
3. flow of Ca2+ into cytocol ---->
   
   1. ---->Ca2+ binds to Ca2+ receptors (ryanodine) on external surface of the SR
   2. opening of Ca2+ channels intrinsic to these receptors
   3. Ca2+ flow  into cytosol --->
4. Inc. cytosolic Ca2+ concin.
5. (multiple steps) ----> contact.
   

-intra. cell Ca activates calmodulin

-Ca2+ : calmodulin activates myo light chain kinase

- Phosporlated = myo binds actin

-Unphosphorylated myo doesn't bind

- myo-P can enter cross-bridge

• Creatine kinase phosphorylates Adp using creatine-phosphate

Creatine Kinase

Creatine-P + ADP <------------> Creatine + ATP

• Oxidative phosphorylation
• Glycolysis
• Usually 5 times the level of creatine-P as ATP
  

• Can pull on muscle and lengthen it
• Release it and the muscle will spring back
• Due to tension from titin filaments being

- 2 sources: 1. Sarcoplasmic Reticulum 2. extracell. Ca2+

- smaller sarcoplasmic reticulum than skele

- action potential trigger release of Ca2+ fr. SR or influx fr. ions channels in plas. mem.

- cell signaling can also trigger influx of Ca2+ fr. ion channels

IMPORTANCE OF ATP BINDING AND HYDROLYSIS

-Binding & hydrolysis is key part of process

-ATP bind to myosin breaks link b/t myosin & actin

-ATP-bound myosin has low affinity for actin

-ATP hydrolysizes to ADP = energizes myosin & stores energy for the conformation change of powerstroke

RIGOR MORTIS

**shows inportance of ATP dissociat. of actin and myosin (step 3  X-bridge)**

-the gradual stiffening of skele. mus. that begins several hrs. after death

-reaches a max. after ~12 hrs.

-Dissapears ~40-60 hrs. after death = muscle tiss. decomposed

-ATP contract. declines b/c nutrient & oxyg. supply = not avail. b/c no circulation

-No ATP = no break b/t myos. & actin = thick + thin filaments still bound

  = thick + thin filaments can't pull past ea. other