Topic 14: Skeletal Muscle Muscle is the material that really sets biomechanics apart from other branches of mechanics 3 Types: skeletal (voluntary) }striated cardiac (involuntary) }striated smooth (involuntary) }unstriated The main difference between skeletal and cardiac muscle is that skeletal muscle can exhibit a sustained ‘tetanic’ contraction whereas cardiac muscle ‘beats.’ 23-Feb-1999 Good framework for a lecture but contains some redundancy. Improve by: 1. remove repetition 2. use state of the art illustrations especially for activation and crossbridge cycle. See Opie and refs therein 3. add some state of the art such as single myosin molecule studies by Yanagida or Spudich 4. scan Netter slides for images of neuromuscular junction 5. Add material on muscle fiber architecture from JAP 1998;85(4):1230-1235 or simlar refs.

Structure of Skeletal Muscle

Structure of Skeletal Muscle Fascicle: Surrounded by collagen sheath Myofibril (1m Ø): 100’s-1000’s per myofiber ~ 1500 thick filaments ~ 3000 thin filaments Muscle cell (fiber): 10-80 mm f multinucleated sarcolemma sarcoplasm sarcoplasmic reticulum striated

Myofibrils 1 m Ø ~1500 thick filaments 12nm Ø ~3000 thin filaments 6 nm Ø surrounded by sarcoplasmic reticulum A (optically anisotropic) band I (optically isotropic) band Z-line

The Sarcomere

Anisotropic Isotropic to polarized light ~ 2.0 m The Sarcomere Anisotropic Isotropic to polarized light ~ 2.0 m

Hexagonal Arrangement of Myofilaments in Cross-Section

Myofilaments Thick myosin filaments (180 myosin molecules polymerized) Thin actin filaments They interdigitate to form the SARCOMERE

Actin F-actin molecule formed from G-actin Twisted with a period of 70 nm - double helix Two strands of tropomyosin Globular troponin molecules (with a strong affinity for Ca2+) attached to tropomyosin strands, every 7 G-actin monomers

Myosin Subdomains: Heavy Meromyosin HMM Light Meromyosin LMM S1-Head Myosin leads protrude in pairs at 180º There are about 50 pairs of cross-bridges at each end of the thick filament The filament makes a complete twist 310º every 3 pairs 14.3 nm internal between pairs

The Crossbridge

Activation The trigger that stimulates muscle contraction is calcium. It is bound at rest to the sarcoplasmic reticulum (SR). When the myocyte is depolarized, Ca2+ leaves SR and binds to the troponin-C subunit on the thin filaments. This causes tropomyosin to move slightly removing a steric restraint at the active site on the thin filament. This switch is very sensitive to Ca2+ concentration (mM).

Excitation-Contraction (EC) Coupling Muscle cells, like nerves, are excitable tissues. They have a negative resting membrane potential owing to the imbalance of and K+ ions across the semi-permeable membrane. This gradient is maintained by the Na-K pump (ATPase).

Excitation-Contraction (EC) Coupling To stimulate excitable tissue: cell membrane is locally depolarized to a threshold level The depolarization amplifies transiently due to changes in membrane permeability to Na+ and K+ This transient is the propagated as a wave Cell acts like a transmission line due to its inherent intracellular conductivity and its membrane capacitance

On each muscle fiber, a nerve ending terminates near the center (at the muscle end-plate). Each nerve has from 2-3 to 150 fibers or more depending on the type of muscle. At the end-plate is the neuromuscular junction. Stimulus is transmitted by neurotransmitter Acetylcholine (mopped up by cholinesterase). The Motor Unit

Energy for Contraction Large amounts of ATP are hydrolysed to from ADP. The more work performed by the muscle, the greater the amount of ATP that is cleaved: the Fenn effect. When the inhibitory effect of the troponin-tropomyosin complex has been removed calcium binding, the heads of the cross-bridges bind with exposed sites on the actin filament. It is assumed that the bond between the head of the cross-bridge and the active site of the actin filament causes a conformational change in the head, thus causing the head to tilt releasing energy that has already been stored in crossbridge head during the previous detachment.

Crossbridge Cycle Once the head of the cross-bridge is tilted, conformational change in the head exposes a site in the head where ATP can bind. One molecule of ATP binds with the head, binding in turn causes detachment of the head from the active site Once the head bound with ATP splits away from the active site, the ATP is itself cleaved by a very potent ATPase activity of the heavy meromyosin. The energy released supposedly tilts the head back to its normal condition and primes it for the next “power stroke”.

Crossbridge Cycle

History of Muscle Contraction

Muscle Architecture Flexor, Extensor, Belly, Tendon, Aponeurosis

Muscle Architecture: Collagen Matrix

Muscle Architectures Parallel (fusiform) Convergent Pennate Circular (areolar)

Muscle Architecture Figure 9.2:2 from textbook. Diagram illustrating (a) parallel-fibered and (b) pinnate muscles. (c) and (d) illustrate pinnate muscle contraction.

Muscle-Tendon Mechanics In most skeletal muscle, fibers attach to tendon plates, or aponeuroses, which then become rounded tendons Interaction between muscle fiber and tendons cannot be neglected Isolated tendon mechanical properties have been studied But we can not consider muscle or tendon properties in isolation Muscle length change is not the same as that of the muscle-tendon complex: muscle fibers of cats shortened by as much as 28% at the expense of the tendon during isometric contractions Muscle fibers do work when there is no net work done by the whole muscle-tendon complex Ito et al., studied relationships between muscle architectural parameters and tendon force using ultrasound Masamitsu Ito, Yasuo Kawakami, Yoshiho Ichinose, Senshi Fukashiro, and Tetsuo Fukunaga. Nonisometric behavior of fascicles during isometric contractions of a human muscle. J Appl Physiol 1998;85(4):1230-1235

Muscle-Tendon Mechanics LEFT: Schematic representation of experimental setup. A dynamometer was used to fix the ankle joint angle at 20° plantarflexion from the anatomic position and measure dorsiflexion torque. Right foot was firmly attached to the footplate of the dynamometer with a strap. An ultrasonic probe was used to obtain sectional images of the tibialis anterior muscle (TA). The TA is a bipennate muscle. RIGHT: Longitudinal ultrasonic images of TA (right, proximal) at 20° plantarflexion under relaxed (top) and moderately tensed (bottom) conditions. Fascicle length (Lf) decreased and pennation angle (q) increased with force.

Cross-Sectional Area and Stress

Skeletal Muscle: Summary of Key Points Skeletal muscle is striated and voluntary It has a hierarchical organization of myofilaments forming myofibrils forming myofibers (cells) forming fascicles (bundles) that form the whole muscle Overlapping parallel thick (myosin) and thin (actin) contractile myofilaments are organized into sarcomeres in series Thick filaments bind to thin filaments at crossbridges which cycle on and off during contraction in the presence of ATP Nerve impulses trigger muscle contraction via the neuromuscular junction The parallel and/or pennate architecture of muscle fibers and tendons affects muscle performance