MUSCLE 3

TOPICS

• Contraction

  • Excitation contraction couplinh

  • Calcium regulates contraction

  • Crossbridge cycling

  • Removal of calcium ends a contraction

• ATP supply in skeletal muscle

Memorize this sequence:

Motor neuron AP

↓

ACh released

↓

Muscle AP

↓

T-tubule depolarization

↓

DHP receptor activated

↓

Ryanodine receptor opens

↓

Calcium released

↓

Calcium binds troponin

↓

Actin-myosin interaction

↓

Contraction

AN INCREASE IN cA2+ TRIGGERS CONTRACTION BY REMOVING THE INHIBITION OF CROSS BRUDGE CYCLING

• What turns muscle contraction on and off?

  • Calcium

• Ca2+ binds low affinity sites on troponin C which induces a conformational change in the troponin complex

  • Causes the troponin complex as well as tropomyosin to move revealing the myosin binding site on the actin

CALCIUMA ND CROSSBRDGE FORMATION

• A muscle action potential reaches the T tubules and causes the sarcoplasmic reticulum to release calcium. Calcium binds to troponin, which moves tropomyosin out the way so myosin can attaches to actin and generate force. To relax the muscle, calcium is pumped back Into the sarcoplasmic reticulum using ATP. Once calcium leaves troponin, tropomyosin blocks the binding site again and contraction stops

  • Calcium release from the sarcoplasmic reticulum turns contraction on and atp powered calcium pumps (SERCA) return calcium to the SR tp turn contraction and allow muscle relaxation

Simple summary

• Once calcium exposes the binding sites on actin, myosin attaches to actin and pulls it toward the centre of the sarcomere. ATP is required for myosin to let go of actin. ATP is then broken down to re-energize the muosin head to it can attach and pull again. This cycles repeats many times, causing the  muscle contract. ATP is absent, myosin cannot detach from acting, leading to rigor (stiffness)

CROSSBRIDGE CYCLE

• Once intracellular Ca2+ is elevated tropomyosin shifts allowing myosin to tightly bind actin

ATP BINDING

• ATP binds to the head of myosin heavy chain reducing affinity of myosin for actin

  • Myosin loses its strong attraction to actin

  • Cross bridgebreaks

ATP HYDROLYSIS

• ATP is broken down to ADP and inorganic phosphate (P1) resulting In the myosin head pivoting arounf hinge into COCKED STATE. The cocked head is now alignhed with and binds to a new actin molecules on thin filament

  • The energy is used to move the myosin head into the COCKED STATE

    • The myosin head bends backwards , energy is stored in the head

      • The head now contains ADP AND Pi

THE POWERSTROKE

• Dissociation of P1 from myosin head strengthen bonds between actin and myosin and triggers power stroke, a conformational change in which the myosin head returns to its uncocked state and while doing so pill the actin filament generating force and motion

  • The myosin head swivels back towards its original position

  • It pulls the actin filament

  • Actin moves towards the  Mline

  • Sarcomere shorten

  • Force is generated

ADP RELEASE

• Dissociation of ADP from myosin causes myosin to remain bound to actin until ATP initiates the cycle again

SLIDING FILAMENT THEORY

• The sarcomere shortens during contraction, actin and myosin do not change length but instead slide past one another

• When a muscle contracts the actin filament are pulled toward the centre of the sarcomere by the myosin heads. The acting and myosin filament themselves do not get shorter. Instead they slide past each other increasing theor overlap. This makes the sarcomere shorter which causes the whole muscle to shorten and produce force

  • Muscle contraction occur because acitn slides past myosin causing the sarcomere to shorten, the I band and H zone decrease in size while the A band stays the same length

TERMINATION OF CONTRACTION

• Termination of contraction requires removal of Ca2+

• Once the AP has subsided Ca2+ must be removed so that the myosin binding site on actin can be covered by tropomyosin

• To contracts

  • High Ca2+ inside the muscles , calcium binds to troponin, tropomyosin moves away, myosin binds actin , contraction occurs

• To relax

  • Calcium must be removes from the cytoplasm, calcium leaves troponin, tropomyosin covers the binding site again , myosin cannot bind actin , relaxation occur

• Ca2+ can be removes to the extracellular space by the Na-Ca exchanger or by the Ca2+ pump which uses ATP

  • Would eventually deplete the cell of any Ca2+, leaving the Sr empty and because of this plays a minor role

SERCA PUMP

• The main way skeletal muscle relaxes: putting Ca2+ back into the sarcoplasmic reticulum

• Mediated by the sarcoplasmic and endoplasmic reticulum Ca2+- ATPase(SERCA)-type Ca2+ pump

• Ca2+ reuptake into the SR

  • Calcium is taken back into the sarcoplasmic reticulum

• High Ca2+ in the SR inhibit this pump

• Ca2+ binding protein exist in SR to delay inhibition

  • These proteins grab calcium and bind it

    • CALSEQUESTRIN AND CALRETICULIN maximize Ca2+ uptake by the SR

    • Up to 50 Ca2_ binding sites per molecule

  • When muscle contraction is finished, calcium must be removes from the cytoplasm. The SERCA pump uses ATP to move calcium back into the sarcoplasmic reticulum. Inside the SR proteins called CALSEQUESTRIN AND CARETICULIN bind and store the calcium. This lowers cytoplasmic calcium, causes the muscle to relax and prepares the muscle for the next contraction

  • Muscle relaxation occurs mainly when SERA uses ATP to pump Ca2+ into the sarcoplasmic reticulum, where calsequestrin and calreticulin store the calcium for future contractions

RIGOR MORTIS

• Why muscles become stiff after death

• Development of rigid muscle several hours after death

• Ca2+ leaks into the sarcoplasm and binds troponin

  • Normally the SR keeps calcium stored

  • After death cell membrane gradually deterioate , SR membranes become leaky

• ATP production stops

  • CA2+ cannot be removes (SERCA pump is ATP powered)

  • ATP needed to release myosin head from actin

  • Remains in latches cross bridge formation until muscles begin to deteriorate

• After death ATP production stops. Calcium leaks outs of the sarcoplasmic reticulum and binds to troponin, exposing the actin binding sites, Myosin attaches to actin but because there is no ATP available myosin cannot detach. The cross bridges become locked in place causing the muscle to become stiff and rigid. This stiffness is called rigor mortis

EXCIATION CONTRACTION COUPLING

• A nerve signal first reaches the muscle and causes a muscle action potential. The muscle does not contract right away because there is a short latent period where calcium is released and binds to troponin. Once enough calcium is present, the muscle contracts and tension increases. As calcium is pumped back into he sarcoplasmic reticulum the muscles releases and the tension decreases

• A single motor neuron action potential triggers a muscle action potential, followed by a short laten period for calcium release, then a muscle twitch consisting of contraction and relaxation phase

  • Latent phase (preparation)

  • Contraction phase (force rises)

  • Relaxation phase (force falls)

MUSCLES NEED A STEADY SUPPPLY OF ATP TO FUNCTION

• Muscles need ATP for

  • Contraction (Myosin ATPase)

  • Relaxation (SERCA- Ca2+ ATPase)

  • Restoring ion gradient after action potentials (Na+/K+ ATPase)

• Sources of ATP

  • Free intracellular ATP (few seconds)

  • ATP formed from phosphocreatine (10 sec)

  • Glycolysis

  • Aerobic (oxygen-requiring) metabolism

• Muscles requires ATP for contraction, relaxation and ion pumping during the first seconds of activity ATP is suplied by stored atp and the phosphocreatine

• Glycolysis

  •  large amount of glucose is stored in muscle cells in the form of glycogen (glycogenesis)

  • When ATP is needed glycogen is then converted back into glucose (glycogenolysis)

  • One glucose molecule can then be broken down to pyruvate by glycolysis resulting in the production of two ATP molecules

  • This process occurs in the absence of oxygen and is therefor termed ANAEROBIC METABOLISM , pyruvate is further converted to lactate

  • Takes place in the sarcoplasm of the muscle

    • Muscles cells tore glucose as glycogen, when more atp is need glycogen is broken down into glucose. The glucose goes through glycolysis in the sarcoplasm producing 2 atp and 2 pyruvate molecules. Because this process does not require oxygen it is called anaerobic metabolism . When oxygen is limited pyruvate is converted into lactate so glycolysis can continue making atp

• AEROBIC (OXYGEN REQUIRING) METABOLISM

  • If oxygen and mitochondria are present oxidative(aerobic) metabolism may take place

  • After glycolysis pyruvate then enters the citric acid cycle producing two more molecules of ATP as well as high energy electrons and H+

  • The high energy electrons and H+ combine with O2 in the electron transport chain to produce an additional 26-28 molecules of ATP

  • Occurs in the mitochondria and oxygen is necessary

  • When oxygen is available, pyruvate produced by glycolysis enters the mitochondria instead of becoming lactate. It is converted into acetyl Coa and enters the citric acid cycle, producing a small amount of ATP and many high energy electron carriers (NADH and FADH2) these carriers deliver electrons to the electron transport chain, where energy is used to generate a large amount of ATP

SOURCES OF ATP

• Free intracellular ATP (first few seconds)

• ATP from creatine phosphate (bout 10 seconds)

• ATP produced through anaerobic metabolism (short term moderate exercise)

• ATP produced through aerobic metabolism (long term exercise)

What fuel muscles burn down during exercise?

• Beta oxidation

  • Burning fat for energy

  • At low exercise intensity

    • muscles use more fat

  • As exercise intensity increases

    • Muscles rely increasingly on carbohydrates (CHO)

• When you're resting or exercising lightly, muscles get most of their energy from fat because fat provides lots of ATP. As exercise becomes harder, muscles needs ATP more quickly so they begin using more carbohydrates (glucose and glycogen). At a very high exercise intensities carbohydrates become the main fuel source because they can produce ATP faster than fat