Skeletal Muscle Physiology PDF

Skeletal Muscle Physiology  Learning Objectives Outline functional structure of skeletal muscle. Outline structure of myoneural junction. Describe excitation-contraction coupling. Define simple muscle twitch. Describe isotonic and isometric skeletal muscle contraction.  Gross Anat...

Skeletal Muscle Physiology  Learning Objectives Outline functional structure of skeletal muscle. Outline structure of myoneural junction. Describe excitation-contraction coupling. Define simple muscle twitch. Describe isotonic and isometric skeletal muscle contraction.  Gross Anatomy of Skeletal Muscle It is called skeletal muscle because it is attached to the skeleton. When it contracts, it moves bones of the skeleton at joints. A skeletal muscle consists of many multinucleated muscle cells called muscle fibers. A single muscle fiber is composed of thousands of contractile filaments called myofilaments. Myofilaments are two types:- – thin (actin) filaments. They have binding site for thick filaments. – thick (myosin) filaments. They have a head that can bind to thin filaments. Gross Anatomy of Skeletal Muscle The cross striation of the muscle  The skeletal muscle appear striated under the microscope. The functional unit of the skeletal muscle is called sarcomere. Sarcomeres are bounded by two lines called Z lines. Each sarcomere has central dark band called A band and two peripheral light bands called I bands. During muscle contraction, the following events occur: – Thin filaments slide along the thick filaments leading to disappearance of I bands, while A bands remain constant. – The two Z lines get close. The myofibrils Proteins of the thin filaments Actin is the structural protein of the thin filament. It possesses attachment sites for myosin. Tropomyosin blocks myosin binding sites on actin. Troponin is composed of 3 subunits: troponin-T (binds to tropomyosin), troponin-I (binds to actin and inhibits contraction), and troponin-C (binds to calcium). –– Under resting conditions, no calcium is bound to the troponin, preventing actin and myosin from interacting. –– When calcium binds to troponin-C, the troponin- tropomyosin complex moves, exposing actin binding site for myosin. Proteins of the thick filaments Myosin has ATPase activity. The splitting of ATP puts myosin in a “high energy” state; it also increases myosin’s affinity for actin. Once myosin binds to actin, the chemical energy is transferred to mechanical energy, causing myosin to pull the actin filament. This generates active tension in the muscle and is commonly referred to as “the power stroke.” If the force generated by the power stroke is sufficient to move the load, then the muscle shortens (isotonic contraction). If the force generated is not sufficient to move the load, then the muscle doesn’t shorten (isometric contraction).  Neuromuscular Transmission The junction between the nerve and the muscle is called myoneural junction. It consists of :- 1. Nerve terminal, which show many granules that contain acetylcholine 2. A space between the nerve terminal & the muscle membrane. 3. Skeletal muscle membrane.  Ca Ca Ca Ca Ca Ca  Events occurring at myoneural junction 1. Release of acetylcholine from motor nerve terminals in the space between the nerve and the muscle. 2. Acetylcholine cross the space between the nerve terminal & the muscle to bind its specific receptors on the skeletal muscle membrane. 3. Acetylcholine cause increased membrane permeability to sodium and generation of action potential and its spread along the skeletal muscle membrane. 4. Depolarization of the skeletal muscle membrane cause release of calcium from its intracellular stores into the sarcoplasm. 5. Calcium cause contractile filaments of the muscle to slide over each other leading to muscle shortening. In this process, thin filaments slide over the thick filaments (ATP is the source of energy needed for sliding of the contractile filaments and muscle contraction). 6. Calcium is then pumped actively back to its intracellular stores leading to muscle relaxation ( ATP is the source of energy needed for calcium reuptake and muscle relaxation ). REGULATION OF CYTOSOLIC CALCIUM The sarcoplasmic reticulum (SR) has a high concentration of Ca2+. Thus, there is a strong electrochemical gradient for Ca2+ to diffuse from the SR into the cytosol. There are 2 key receptors involved in the flux of Ca2+ from the SR into the cytosol: dihydropyridine (DHP) and ryanodine (RyR). DHP is a voltage-gated Ca2+ channel located in the sarcolemmal membrane. Although it is a voltage-gated Ca2+ channel, Ca2+ does not flux through this receptor in skeletal muscle. Rather, DHP functions as a voltage-sensor. When skeletal muscle is at rest, DHP blocks RyR. RyR is a calcium channel on the SR membrane. When the muscle is in the resting state, RyR is blocked by DHP. Thus, Ca2+ is prevented from diffusing into the cytosol. Sequence 1. Skeletal muscle action potential is initiated at the neuromuscular junction. 2. The action potential travels down the T-tubule. 3. The voltage change causes a conformation shift in DHP (voltage sensor), removing its block of RyR. 4. Removal of the DHP block allows Ca2+ to diffuse into the cytosol (follows its concentration gradient). 5. The rise in cytosolic Ca2+ opens more RyR channels (calcium- induced calcium release). 6. Ca2+ binds to troponin-C, which in turn initiates cross-bridge cycle, creating active tension. 7. Ca2+ is pumped back into the SR by a calcium ATPase on the SR membrane called sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA). 8. The fall in cytosolic Ca2+ causes tropomyosin to once again cover actin’s binding site for myosin and the muscle relaxes, provided of course ATP is available to dissociate actin and myosin.  Mechanism of relaxation: The effect of acetylcholine is terminated by the cholinesterase enzyme at the neuromuscular junction. As there is no longer action potential, calcium is pumped back to the S.R by calcium pump (active). Myosin –binding sites on actin will be covered again. ALTERING FORCE IN SKELETAL MUSCLE Mechanical Response to a Single Action Potential The figure below illustrates the mechanical contraction of skeletal muscle and the action potential on the same time scale. Note the sequence of events: action potential causes Ca2+ release. The release of Ca2+ evokes a muscle contraction (twitch).  Summation and Recruitment Under normal circumstances, enough Ca2+ is released by a single muscle action potential to completely saturate all the troponin-C binding sites. This means that all available cross-bridges are activated and thus force cannot be enhanced by increasing cytosolic Ca2+. Instead, peak force in skeletal muscle is increased in 2 ways: summation and recruitment. Summation Because the membrane has repolarized well before force development, multiple action potentials can be generated prior to force development. Each action potential causes a pulse of Ca2+ release. Each pulse of Ca2+ initiates cross-bridge cycling and because the muscle has not relaxed, the mechanical force adds onto (summates) the force from the previous action potential. This summation can continue until the muscle tetanizes in which case there is sufficient free Ca2+ so that cross- bridge cycling is continuous. Recruitment A single alpha motor neuron innervates multiple muscle fibers. The alpha motor neuron and all the fibers it innervates is called a motor-unit. Recruitment means activating more motor units, which in turn engage more muscle fibers, causing greater force production.  The muscle is not shortened The force developed in the muscle is maximal.  The muscle is shortened The force developed in the muscle is not maximal.