18. Molecular aspects of muscle contraction and electromechanical coupling Flashcards
What should be mentioned in this topic?
- Molecular aspects of muscle contraction and electromechanical coupling
Electro-mechanical Coupling
Four Stages of Electro-Mechanical Coupling
From AP to muscle contraction
The Triad
Receptors in the T-tubule
Sarcomer: The „Sliding Filament” Mechanism
Molecular Structure of Sarcomer:
-Actin
-Myosin
The Cross-Bridge Cycle
ATP related conformational changes at cross-bridge cycle
ATP and Ca2+ dependence of the contraction
The „Ratchet Mechanism”
The removal of calcium (from cytosol)
From neural activation to muscle contraction (summary)
Electro-mechanical Coupling
Definition: The process which starts with the myogenic AP and ends with the contraction of the muscle fibre is usually called electro-mechanical coupling (followed by relaxation).
- Neural action potential is transferred to the muscle fibre at the myoneural junction area.
- This result in a growing AP on the myolemma (the cell membrane of a striated muscle fiber cell)
- The electrical signal of the myolemma finally reaches the triad through the system of T-tubuli, where it is transformed into the calcium-signal.
-The latter triggers contraction, (muscle twitch) occurs.
From AP to muscle contraction
(picture and explaination)
- Action potencial (AP) reaches the myolemma from the NMJ
- AP reaches the L-type (voltage gated) Ca2+-channels in the T-tubuli, the L-type channels open
- Because the L-channels open, the ryanoid-Ca2+-s will also open (due to the conformational change):
- From the sarcoplasmatic reticulum (SR) a lot of Ca2+ will get into the IC part of the cell
- The Ca2+-channels on the myolemma will also open (Ca2+-influx from the EC )
- Result: IC Ca2+ level will be really high around the sarcomer
The Triad
- The basis of the excitation-contraction coupling is the triad.
- This part of myocyte is where the T-tubule of myolemma is closest to the IC sarcomplasmic reticulum.
- As an effect of the neural AP the conformation of T-tubule voltage-sensing receptor will change.
- This opens the closely adjoining T-type ryanodin calcium channel on the SR membrane: a high amount of calcium will be released from SR into the intracytoplasmic (myoplasmic) space.
- Calcium rapidly opens the rest of SR calcium channels (so called: calcium-dependent calcium channels).
- The result is the increase of calcium-concentration, which triggers the cross-bridge cycle.
Sarcomer: The „Sliding Filament” Mechanism
Main component is called G-actin, which forms polarized actin-fibres.
In resting state, tropomyosin covers active sites on the surface of actin molecule which could stimulate ATPase activity of myosin.
A complex protein, troponin-complex, binds to tropomyosin. Tn-I (inhibitory) and Tn-T (tropomyosin binding) are parts of troponin-complex holding tropomyosin in position. Tn-C (calcium-binding) part is calcium free in resting conditions.
It is activated after calcium binding and, through consecutive conformation changes it displaces tropomyosin fibre. Tropomyosin slides into the groove of the two stranded actin helix. The Cross-bridge cycle starts.
The sliding of actin and myosin microfilaments on each other is considered to be the basic mechanism of muscle contraction. The fundamental process of the sliding phenomenon is the shifting of myosin head by 45 degrees which occurs after the development of connections between myosin head and actin microfilament.
Molecular Structure of Sarcomer: myosin
Myosin bundle consists of 6 elementary myosin molecules. The two heavy chains (HC) are composed of an elongated alpha helix, and a globular part.
The globular part forms the head of the myosin which has an angle of 90 degrees with the alpha helices. The head region may bend with a maximal angle of 45 degrees. This part contains chains responsible for ATP binding and splitting (myosin isotipes).
There are two light chains (LC) connected to the head regions of both alpha-helices. The LC has ATPase activity.
Cross bridge cycle - basics
The number of cross-bridges formed between actin and myosin determine the amount of tension that a muscle fiber can produce. Cross-bridges can only form where thick and thin filaments overlap, allowing myosin to bind to actin. If more cross-bridges are formed, more myosin will pull on actin and more tension will be produced
Actin and myosin is the connection needed to turn chemical energy into mechanical energy, which is simply known as movement by contracting and relaxing.
Why is calcium important for muscle contraction?
During contraction of a muscle, calcium bind to troponin. This moves tropomyosin out of the way and uncovers binding sites for myosin on the actin myofilaments.
Milk fever
Milk fever is primarily found in dairy cattle, and is characterized by reduced blood calcium levels. Almost all cases occur within one day of calving because milk and colostrum production drain calcium from the blood, and some cows are unable to replace the calcium quickly enough.
Treatment generally involves calcium injection by intravenous, intramuscular or subcutaneous routes.
When lacking calcium there is no one which can move the tropomyosin. The binding sites will remain blocked, and myosin isn´t able to bind to actin, leading to a permanent relaxation of the muscle
Why is ATP important for muscle contraction?
The bond between actin and the myosin head is broken when an ATP molecule binds to the myosin head. The ATP is broken down to ADP and phosphate, releasing energy which is stored in the myosin head and will be used later for movement.
ATP is needed to detach the cross-bridge. Without ATP, calcium remains bound to troponin, and the cross-bridge stays attached. After we die, our muscles enter into what we call rigor mortis, as our cells no longer make ATP. Eventually, the corpse relaxes as the proteins within the muscle degrade and the cross-bridge breaks down.
As ATP is absent, there must be a breakdown of muscle tissue by enzymes during decomposition. As a process of decomposition, the myosin heads are degraded by the enzymes, allowing the muscle contraction to release and the body to relax. This is because, even tho oxygen no longer is present, the body may continue to produce ATP via anaerobic glycolysis, but glycogen will decrease, as well as the concentration of ATP
Removal of calcium
Muscles don’t stay contracted all the time. Eventually, the neurons quit stimulating the muscle, and the contraction stops. If calcium couples excitation with contraction, it would make sense that removing the calcium would then stop contraction. Calcium removal causes relaxation. ATP provides energy to pump, or actively transport, the calcium back into the sarcoplasmic reticulum.
The triad (picture)
From AP to muscle contraction ( 1/2 pictures)
From AP to muscle contraction (2/2)
Receptors in the T-tubule (picture and explaination)
As an effect of the AP, a modified calcium channel, the L-type (dihydropyridine or DHP) receptor undergoes a conformational change. On the intracellular side it physically connects with the membrane of the terminal cisternae, where the T-type (ryanoid) calcium channels can be found. After L-type receptor activation due to this connection the T-type channels will also open.
Receptors in the T-tubule (closed and opened state)
Molecular Structure of Sarcomer: Actin (picture)
Molecular Structure of Sarcomer: myosin
Sarcomer: The „Sliding Filament” Mechanism (picture)
ATP related conformational changes at cross-bridge cycle
(picture, 1/4)
ATP related conformational changes at cross-bridge cycle
(picture, 2/4)
ATP related conformational changes at cross-bridge cycle
(picture, 3/4)
ATP related conformational changes at cross-bridge cycle
(picture, 4/4)
The cross-bridge cycle (picture)
The cross-bridge cycle (picture)
ATP and Ca2+ dependence of the contraction (picture)
The „Ratchet Mechanism” (picture)
The removal of calcium (from cytosol) (picture)
From neural activation to muscle contraction (summary) (picture 1/2)
From neural activation to muscle contraction (summary) (picture 2/2)
