Ch 1 - Skeletal Muscle Flashcards
Excitation-contraction coupling
AP -> binding of myosin and actin -> contraction
Myosin
• Thick Filaments
• Large molecular weight
• Six polypeptides
- 2 heavy-chain myosin
• alpha-helical "tail"
- 2 pairs of light chains
• Globular "heads"
>> Actin-binding siteThin Filaments
• Anchored at the Z lines within the I bands
• Components
- Actin = has myosin-binding sites
- Tropomyosin = blocker
Tropomyosin
- a filamentous protein
- runs along the groove of each twisted actin filament
- at rest, blocks the myosin-binding sites on actin, to prevent contraction
- must be removed for contraction to occur
Troponin
- Complex of 3 globular proteins:
• Troponin T = attaches the troponin complex to tropomyosin
• Troponin I = along w/ tropomyosin, inhibits the interaction of actin and myosin by covering the myosin-binding site on actin
• Troponin C = Ca2+ binding site
Troponin T
- T for tropomyosin
- Attaches the troponin complex to tropomyosin
Troponin I
- I for inhibition
- along w/ tropomyosin, inhibits the interaction of actin and myosin by covering the myosin-binding site on actin
Troponin C
- C for Ca2+
- Ca2+ binding site
Sarcomere
- Basic contractile unit
- Delineated by Z disks (goes from one z disc to another)
- Full central A band with half of two I bands on either side
A bands
- located in the center of the sarcomere
- contain the thick (myosin) filaments
- thick and thin filaments may overlap in the A band; potential sites of cross-bridge formation
I bands
- located on either side of the A band
- contain the thin (actin) filaments, intermediate filamentous proteins, and Z disks
Z disks
- Delineates the ends of each sarcomere
Bare Zone
- NO POTENTIAL FOR CROSS-BRIDGING
- Center of each sarcomere w/ no overlapping filaments
M line
- Bisects unit in 1/2; divides the sarcomere in half
Cytoskeletal Proteins of Sarcomere
- Architectural proteins ensuring that the thick and thin filaments are aligned correctly and at proper distances w/ respect to each other
- “Scaffold”
Titin
- longitudinal cytoskeletal protein
- associated w/ thick filaments
- maintains the integrity of the sarcomere during contraction
- center the thick filaments in the sarcomere
- biggest protein in the body
- extends from the M lines to the Z disks
Nebulin
- longitudinal cytoskeletal protein
- associated w/ thin filaments
- serves as a “molecular ruler,” setting the length of thin filaments during their assembly
alpha-Actinin
anchors the thin filaments to the Z disk
Dystrophin
anchors the myofibrillar array to the cell membrane
Duchenne Muscular Dystrophy
- due to a deletion of the DMD gene (Xp21); dystrophin
- symptoms usually appear in males before age 6
- progressive proximal muscle weakness of the legs and pelvis associated with a loss of muscle mass is observed first
- eventually weakness will spread to arms, neck, and other areas
- Gowers’ maneuver
- Pseudohypertrophy of calf = it increases in size and from the outside it looks like muscle growth but it is actually fat & connective tissue
- few survive beyond 20
Becker’s muscular dystrophy
- milder form of DMD
- due to a mutation, not deletion
Transverse Tubules
- conducts AP to interior of fiber allowing release of Ca2+ from Sarcoplasmic Reticulum
- communicates with the Sarcoplasmic Reticulum via the dihydropyridine receptor at the terminal cistern of the Sarcoplasmic Reticulum
The transverse tubules communicate with the SR vi the
Dihydropyridine receptor at the terminal cistern of the SR
Sarcoplasmic Reticulum
- Site of storage and release of Ca2+
- Ryanodine receptor = channel thru which Ca2+ is released
- Calsequestrin = a low-affinity, high-capacity Ca2+ binding protein within the SR
- Ca2+ ATPase (SERCA) = pumps Ca2+ into SR
Steps in Excitation-Contraction Coupling in Skeletal Muscle
AP in the muscle cell membrane initiate depolarization of the T Tubules -> causes a critical conformational change in its voltage-sensitive dihydropyridine receptor opening the Ca2+ release channels (ryanodine receptors) on the nearby SR into the intracellular fluid -> Intracellular [Ca2+] rises to above 10^-7 M -> Ca2+ binds to troponin C on the thin filaments leading to cross bridging events
Events in Cross Bridging
Ca2+ binds to Troponin C on the thin filaments -> Tropomyosin is moved out of the way -> actin & myosin bind, allowing thick and thin filaments to slide over each other, and ATP is hydrolyzed -> cross bridges break and a new molecule of ATP binds to the myosin head to begin a new cycle
What happens during muscle cell relaxation?
- Ca2+ is reaccumulated in the SR by the Ca2+ ATPase of the SR membrane (SERCA)
- Ca2+ concentration decreases to less than 10^-7 M -> insufficient Ca2+ for binding to troponin
- Ca2+ is released from troponin C
- Tropomyosin returns to its resting position preventing myosin interaction w/ actin
Length-Tension Relationship
Refers to the effect of muscle fiber length on the amount of tension the fiber can develop
Isometric contraction
A contraction in which a muscle exerts force (tension) but does not change in length
The muscle is allowed to develop tension at a preset length (called preload) but is not allowed to shorten
Yoga & stretching
Isotonic contraction
Shortening of muscle at a constant afterload
Actually doing reps with the barbell
Passive Tension
Tension developed by simply stretching a muscle to different lengths
Generate greatest tension at its resting length; tension of an unstimulated muscle
Active Tension
Represents the active force developed during cross-bridge cycling
Active tension = total tension - passive tension
Proportional to the number of cross-bridges that cycle
Force-Velocity Relationship
The velocity of shortening reflects the speed of cross-bridge cycling
As the afterload on the muscle increases, the velocity will be decreased b/c cross-bridges can cycle less rapidly against the higher resistance
As the afterload increases to even higher levels, the velocity of shortening is reduced to zero
Smooth Muscle
- unstriated; thick & thin filaments, while present, are not organized in sarcomeres
- found in GI Tract, bladder, uterus (strongest muscle in body), bronchioles, etc.
Types of Smooth Muscle
Unitary Smooth Muscle: located in GI tract, bladder, uterus; contain gap junctions which allows for the coordinated fashion of organ contraction, permits electrical coupling between cells. Slow waves which sets a characteristic pattern of APs within an organ, which then determines the frequency of contractions
Multiunit Smooth Muscle: located in iris, ciliary muscles of the lens, and in the vas deferens. Each muscle fiber behaves as a separate motor unit (similar to skeletal muscle), and there is little or no coupling between cells. Densely innervated by postganglionic fibers of the para & sympathetic nervous systems
What is the regulating factor of the myosin-actin bridges in smooth muscle?
Calmodulin rather than troponin is the regulating factor of the myosin-actin bridges
- Ca2+ binds to calmodulin instead of troponin C
- In turn, Ca2+ - calmodulin regulates myosin-light-chain kinase, which regulates cross-bridge cycling
Steps in Excitation-Contraction Coupling in Smooth Muscle
- AP occur in the smooth muscle cell membrane
- Opening of voltage-gated Ca2+
- Ca2+ flows down its gradient into the cell (intracellular Ca2+ concentration increases)
- Ca2+ binds to calmodulin
- The Ca2+ - calmodulin complex binds to & activates myosin-light-chain kinase
- Myosin becomes phosphorylated
- Cross-bridge formation
Relaxation of smooth muscles occurs when
The SR re-accumulates Ca2+, via the Ca2+ ATPase, and lowers the ICF [Ca2+] below the level necessary to form Ca2+ - calmodulin complexes
Mechanisms that Increase Intracellular Ca2+ Concentration in Smooth Muscle
- Voltage-gated Ca2+ channels are sarcolemmal Ca2+ channels that open when the cell membrane potential depolarizes
- Ligand-gated Ca2+ channels also are present in the sarcolemmal membrane
- IP3-gated sarcoplasmic reticulum Ca2+ channels also are opened by hormones & neurotransmitters
- associated w/ thick filaments
- maintains the integrity of the sarcomere during contraction
- center the thick filaments in the sarcomere
Titin
- associated w/ thin filaments
- serves as a “molecular ruler,” setting the length of thin filaments during their assembly
Nebulin
Calsequestrin
A low affinity, high capacity Ca2+ binding protein within the SR
At rest, by binding to Ca2+, intracellular Ca2+/free Ca2+ is maintained low
