Muscle physio Flashcards
What are the proteins in the Sarcomere?
Titin: The largest protein of the body. Contains one spring-like protein chain. It originates form Z-lines and ends at myosin bundles. Titin ensures a precise return of actin and myosin bundles to their original position.
Nebulin: determine the direct and placement of actin polymerization during the developemt of the Sarcomere. It protects the developed actin fibre form rearranging effect of other actin-binding proteins.
Alpha-actinin: Creates the Z-band. Is a net-like protein. Provides a binding site for the actin complexes orienting toward the inner part of the sarcomere.
What is a G-actin?
It is the main component of the actin-complex. It forms polarized actin-fibres winding up as double helix.
What is Tropomyosin?
Exisits on the surface of the helix. In resting state, it covers active sites (Amino Acid Sequences) on the surface of actin molecule which could stimulate ATPase activity of myosin.
What is Masking?
It takes place when a complex protein, troponin-complex, binds to tropomyosin.
Tn-I (ihibitory) and Tn-T (tropomyosin bining) parts of troponin complex holding tropomyosin in position.
Tn-C (calcium-binding) part is calcium free in resting condition.
How is Tn-C activated?
After calcium binding and through conformation changes it displaces tropomyosin fibre. Tropomyosin then slides into the groove of the two stranded actin helix and prevoisuly masked myosin-binding (ATPase) amino acid sequences become uncovered on the surface of the actin. Cross-bridge cycle starts.
What do the myosin consist of?
6 elementary myosin molecules. Two heavy chains (HC) are composed of an elongated alpha-helix and a globular part. The globular part forms the head of the myosin (cross-bridge) which has an angle of 90* with the alpha helicec. There are two light chains (LC) connecteed to the head regions of both alpha-helicec. The LC has ATPase activity.
Function of the Myosin
The head region may bend with a maximal angle of 45*- this part contains chanis responsible for ATP binding and slitting (myosin isotipes).
Three types of ATPase occur: LC-1, LC-2 (in fast-twich type) and LC-3 (in slow-twich type).
Explain the sliding filament mechanism
The fundamental process is the shifting of myosin head by 45* which occurs after the development of connections between myosin head and actin microfilament. This event has a very short time, but it has several steps:
1: Calcium ions bind to Tn-C´s, then tropomyosin molecules will move.
2: Actin and myosin bind to each other, ATPase is activated, sliding occurs and connection between actin and myosin is releases.
3: myosin head binds ATP and will berepositioned toits original conformation.
If Ca2+ is present, then a new cycle takes place. If IC calcium-signal is terminated, the cross-bridge cylce stops.
What is the Asynchronous cylces?
it results in the apporoaching of Z-bands to each other, and results in the shortening of the sarcomere length and the muscle itself.
This also means that the Myosin filament cant “fall back” - > continous contraction.
Explain the Cross-bridge Cycle
The initial step is the development of Calcium signal. Calcium is released from the sarcoplasmic reticulum after neural AP is transmitted to the muscle. (explain calcium transient). As an effect of calcium ions, actin-myosin connection is formed. Actin activates myosin, which (due to its ATPase activity) splits the boud ATP and energy is released. With that energy myosin head moves, and because it binds actin Z-lines also moves towards the center of the sarcomere (= contraction).
What is Calcium transient and where does it happen?
It happens in the Cross-Bridge cycle. Calcium is released from the sarcoplasmic reticulum after neural AP is transmitted to the muscle. Concentration of calcium in the intracytoplasmic space is 1000 times increased. Rising Ca2+ levels triggers a number of Calcium Re-pumping mechanisms, which result in down regulation of the calcium increase (leading to Ca2+ elimination from the cytoplasm). Therefore Ca2+ conc. near the sarcomere falls down to the micromolar level again = this is called the calcium transient.
The following events of muscle contraction (after cross-bridge cycle) depends on?
The presence of ATP in the system.
If there is no more ATP in the system: Actin binds myosin heads (in 45*) by myosin cannot dissociate from actin and muscle enters a sustained, inactive, contractile state. this happens when ATP stores exhaust after death and muscle spasm happens (=rigor mortis).
And they depend on the availability of calcium! (explain)
The function of calcium in the event of muscle contraction:
If calcium is present: the cycle restarts again and again. If there is no calcium present, tropomyosin slides over the myosin activating part of actin and the muscle relaxes. In this case myosin heads bind ATP, become rich in energy and form a 90* angle with the longitudinal axis of myosin molecules.
ATP related conformational changes at cross-bridge cycle
Step 1:
F-actin and tropomyosin.
Basic situation = myosin head (cross-bridge) is charged.
90*
Relaxation, Resting
ATP related conformational changes at cross-bridge cycle
Step 2:
Ca, ADP, Pi..
AP result in Ca realease, TnC-Ca pulls of Tropomyosin, myosin binding sites are now available. Cross bridge binds to Actin, energy deliberated. = Power-stroke-1… 40*
Power-stroke 2= ADP dissociation resulting in furhter deliberation. 45*
End result is contraction = lowest energy status.
ATP related conformational changes at cross-bridge cycle
Step 3:
If ATP is present - head binds ATP again. Energy is deliberated, therefore the head is back to 90*, this is the “cocked head” status (rich in energy).
In the same time Ca is removed therefore Actin and Myosin are detached.
Relaxation = te highest energy saturation.
Explain electro-mechanical coupling
Neural action potenital is transferred to the muscle fibre at the myoneural junction area, resulting in a propagating AP on the myolemma. The electrical signal of the myolemma finally reaches the triad through the system of T-tubuli, where it is transformed into the calcium-signal. This triggers the mechanical response of the muscle = contraction occurs.
Explain the steps in electromechanical coupling:
- Action potential reaches the myolemma from the NMJ.
2: AP reaches the L-type (voltage gated) Ca2+-channels in the T-tubuli, the L-type channel open.
3: Because the L-channels open, the ryanoid-Ca2+ will also open.
4: From the sarcoplasmic reticulum (SR) a lot of Ca2+ will get into the IC part of the cell.
5: the Ca2+-channels on the myolemma will also open (Ca2+ influx from the EC).
6: result = IC Ca2+ level will be really high around the sarcomer
Explain the steps of Electromechanical coupling from AP to contraction
- Ca release thorugh the funtion of the TRIAD (T-tubules + two SR terminal cystern.
2: Activation of muscle proteins (Ca initiates the connection between Tropomyosin- Tn complex leading to the formation of Acto-myosin complex).
3: Muscle contraction. If Ca is available there will be continuous power strokes of cross bridges creating contraction through “walk-along” mechanism.
4: Relaxation. Follows the process (Ca elimination from IC space either:
a) Na/Ca antiport mechanism (to the EC space)
b) ATP dependent Ca-pump to the SR
c) And/or to other compartments (i.e mitochondria)
What are the potential dependent Ca-channels in T-tubul membrane:
L-type sensors (channel): which can be blocked by dihydropyridine, DHP.
T-type (ryanoid) Calcium channels: which open/close depending on their conformational state.
What is the morphological basis of the excitation-concentration coupling?
The triad
What happens in the Triad?
this is where T-tubule of he myolemma is closest to the IC sarcoplasmic reticulum. As an effect of the AP, the conformation of T-tubule voltage-sensing receptor (DHP or L-type calcium channel) is changed. This opens the T-type ryanodin calcium channel on the SR membrane: a high amount of Ca2+ is released from the RS into the intracytoplasmic space.
Thorugh a positive feedback, Ca opens the rest of the SR ca channels. All these result the increase of calcium-concentration which triggers the cross-bridge cycling.
The removal of Calcium from the cytosol
- Sodium/calcium ion antiporter between myolemma/EC spaces removing calcium with a secondary active transport mechanism.
2: Active calcium pumping to the SR by active ATP dependent calcium pump.
3: other sequesters (organelles compartmentalizing calcium feks mitochondria or small vesicles.
Chemical composition of muscle tissue:
Water: 75%
Protein: 20%
- Structural proteins (contrctile 50%, other 20%)
- soluble proteins (albumin 20%, enzymes 10%).
Other: 5%
- ATP mmol/kg (skeletal muscle 5, cardiac muscle 1.5, smooth muscle 2).
- Creatine phosphate mmol/kg (skeletal 20, cardaic 2, smooth 0.7).
Types of striated/skeletal muscle:
Pink, white and/or red.
Phasic type- fast twitch muscle fiber:
Pink and white muscle types
Tonic type- slow twitch muscle fiber:
Red muscle type.
Characteristics of Pink muscle types:
ATPase type: fast SR pump: fast Junction/fibre: 1:1 T-system: developed Muscle AP/neural AP: exists/very frequent. contrac. time m/s: 20 Metabolism: mixed Fatigue: slow Fibre length: intermediate
Characteristics of White muscle type:
ATPase type: fast SR pump: fast Junction/fibre: 1:1 T-system: very developed Muscle AP/neural AP: exists/very frequent. contrac. time m/s: 10 Metabolism: Anaerobic Fatigue: Fast Fibre length: very long
Characteristics of Red muscle type:
ATPase type: slow SR pump: slow Junction/fibre: "en grappe"-type T-system: not developed Muscle AP/neural AP: no/rare contrac. time m/s: 200 Metabolism: Oxidative Fatigue: No Fibre length: very short
Muscle hypertrophy
Involes an increase in seize of skeletal muscle through a growth in size of its component cells.
Two factors that contribute to hypertrophy:
- Sarcoplasmic hypertrophy, which focuses on increased muscle glycogen storage.
- myofibrillar hypertrophy which focuses on increased myofibril size.
Energy source of muscle functioning
- Both contraction + relaxation need ATP:
ATP concentration of myocyte 5mmol/l, covers the oxygen need for 2-3sek. - Concentration of Myocyte CRP: 20mmol/l, energy supply for 20-30 sek.
Energy source for Anaerob glycolysis - muscle functioning can be:
- Glycogen: for fast movement, glycogenolysis.
- Glucose: for prolonged, long term contraction.
- Anaerob glycolysis: during heavy physical activity
the source is glucose, the end-product: Lactic acid, through piruvate.
Oxygen dept
Energy sources for Oxidative Phosphorlation of muscle functioning can be:
- Pyruvate is transformed to AcCoa (and not to lactate)
- Produces 36 ATP and CO2
- Energy source of very long-term muscle activity
No oxygen dept.
What will happen to the muscles that cover most of their energy needs by anaerobic glycolysis?
They will resynthesize previously depleted energy stores after work: in this phase resynthesis is going under Aerobic conditions. Muscles shows increased oxygen consumption.
What are the elements of macroscopic investigation of muscle function?
- Elements of Contraction (Contracting Component) CC = Sarcomer.
- Elastic elements (SEC; serial elastic components, PEC; parallel to tendons)
Types of contraction:
- Twitch
- Isotonic contraction (constant tension, regular physiological activity)
- Isometric contraction (tension is changed, but not the length)
- Auxotonic: working against increasing tension, resistance
- Preload: muscle length is adjusted with (pre)load, then isotonic contraction.
- Afterload: contraction begins with isotoic, then blocking of contraction with a load.
Twitch
To an appropriate stimulus muscle answers with contraction: a muscle twitch occurs. After the arrival of AP myoplasmatic reticulum calcium concentration increases, contraction takes place.
Elements (macroscopic examination of muscle function)
During stimulation, due to the contraction of CC, first the SEC elements will reach equilibrium with the load (only the tension is increased). followed by shortening with constant tension.
Isotonic contraction
Muscle shortens with constant tension
Isometric contraction
When only tension is changed but not the length of the muscle.
All or none law
Applies for single fiber only (myocyte). Adequate stimulus (treshold) causes maximal contraction. Inadequate stimulus (below treshold) - no contraction. The amplitude of contraction does not change with the streght of stimulus - contraction is always the same.
Quantal (motor unit) summation:
in a given muscle more and more fibers re contracted due to increased frequency of AP, even the fibers with increased-treshold are contracting.
Contraction (frequency) summation:
in case of repetitive stimulu (increased frequency of AP) there will be additional Ca release before the end of Ca transient. The result is increased amplitudes of contraction, due to extra Ca release, while Ca is still present.
Staircase effect:
(warming up) if new stimuli arrive immediately after the end of the twitch, the new contractions have increasing amplitudes. the reason: increasing efficiency of the ion gated. frequency of AP does not change the reason is the summation of remaining Ca.
Tentaus:
Additive effect. extremely increased frequency of stimuli - two forms: incomplete, then complete tetanus. extreme ca release.
When can length-tension curve be obtained?
when one stimulates (with maximal single impulse) muscles, which are passively stretched with varying loads.
How can we construct the area where muscles execute normal physical work?
As a result of Isometric, Isotonic, Preload and afterload experiments.