Destruction of Acetylcholine ACh bound to ACh receptors is quickly destroyed by the enzyme acetylcholinesterase This destruction prevents continued muscle fiber contraction in the absence of additional stimuli Events at the neuromuscular junction Generation of an action potential

Excitation-Contraction Coupling

Figure 9.10 Synaptic cleft vesicle 1 ACh SR tubules (cut) SR 2 6 3 ADP Pi Net entry of Na+ Initiates an action potential which is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma SR tubules (cut) Synaptic cleft vesicle Axon terminal ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca2+ release from terminal cisternae of SR into cytosol. Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed. Contraction; myosin heads alternately attach to actin and detach, pulling the actin filaments toward the center of the sarcomere; release of energy by ATP hydrolysis powers the cycling process. Removal of Ca2+ by active transport into the SR after the action potential ends. SR Tropomyosin blockage restored, blocking myosin binding sites on actin; contraction ends and muscle fiber relaxes. Ca2+ 1 2 3 4 5 6 Figure 9.10

Figure 9.10 Synaptic cleft vesicle ACh Axon terminal ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. Figure 9.10

Figure 9.10 Synaptic cleft vesicle 1 ACh Net entry of Na+ Initiates an action potential which is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma Synaptic cleft vesicle Axon terminal ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. 1 Figure 9.10

Figure 9.10 Synaptic cleft vesicle 1 ACh SR tubules (cut) SR Ca2+ 2 Net entry of Na+ Initiates an action potential which is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma SR tubules (cut) Synaptic cleft vesicle Axon terminal ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca2+ release from terminal cisternae of SR into cytosol. SR Ca2+ 1 2 Figure 9.10

Figure 9.10 Synaptic cleft vesicle 1 ACh SR tubules (cut) SR 2 3 Ca2+ Net entry of Na+ Initiates an action potential which is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma SR tubules (cut) Synaptic cleft vesicle Axon terminal ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca2+ release from terminal cisternae of SR into cytosol. Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed. SR Ca2+ 1 2 3 Figure 9.10

Figure 9.10 Synaptic cleft vesicle 1 ACh SR tubules (cut) SR 2 3 Ca2+ Net entry of Na+ Initiates an action potential which is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma SR tubules (cut) Synaptic cleft vesicle Axon terminal ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca2+ release from terminal cisternae of SR into cytosol. Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed. Contraction; myosin heads alternately attach to actin and detach, pulling the actin filaments toward the center of the sarcomere; release of energy by ATP hydrolysis powers the cycling process. SR Ca2+ 1 2 3 4 Figure 9.10

Figure 9.10 Synaptic cleft vesicle 1 ACh SR tubules (cut) SR 2 3 Ca2+ Net entry of Na+ Initiates an action potential which is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma SR tubules (cut) Synaptic cleft vesicle Axon terminal ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca2+ release from terminal cisternae of SR into cytosol. Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed. Contraction; myosin heads alternately attach to actin and detach, pulling the actin filaments toward the center of the sarcomere; release of energy by ATP hydrolysis powers the cycling process. Removal of Ca2+ by active transport into the SR after the action potential ends. SR Ca2+ 1 2 3 4 5 Figure 9.10

Figure 9.10 Synaptic cleft vesicle 1 ACh SR tubules (cut) SR 2 6 3 ADP Pi Net entry of Na+ Initiates an action potential which is propagated along the sarcolemma and down the T tubules. T tubule Sarcolemma SR tubules (cut) Synaptic cleft vesicle Axon terminal ACh Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca2+ release from terminal cisternae of SR into cytosol. Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed. Contraction; myosin heads alternately attach to actin and detach, pulling the actin filaments toward the center of the sarcomere; release of energy by ATP hydrolysis powers the cycling process. Removal of Ca2+ by active transport into the SR after the action potential ends. SR Tropomyosin blockage restored, blocking myosin binding sites on actin; contraction ends and muscle fiber relaxes. Ca2+ 1 2 3 4 5 6 Figure 9.10

Sequential Events of Contraction Cross bridge formation – myosin cross bridge attaches to actin filament Working (power) stroke – myosin head pivots and pulls actin filament toward M line Cross bridge detachment – ATP attaches to myosin head and the cross bridge detaches “Cocking” of the myosin head – energy from hydrolysis of ATP cocks the myosin head into the high-energy state PLAY InterActive Physiology ®: Sliding Filament Theory, pages 3-29

Figure 9.12 ATP ADP hydrolysis Pi Myosin head (high-energy configuration) Myosin head attaches to the actin myofilament, forming a cross bridge. Thin filament As ATP is split into ADP and Pi, the myosin head is energized (cocked into the high-energy conformation). Inorganic phosphate (Pi) generated in the previous contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. (low-energy As new ATP attaches to the myosin head, the link between myosin and actin weakens, and the cross bridge detaches. Thick filament 1 4 2 3 Figure 9.12

Figure 9.12 Myosin head ADP (high-energy configuration) Pi 1 Myosin head attaches to the actin myofilament, forming a cross bridge. 1 Figure 9.12

Figure 9.12 Myosin head ADP (high-energy configuration) Pi 1 Myosin head attaches to the actin myofilament, forming a cross bridge. Inorganic phosphate (Pi) generated in the previous contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. 1 2 Figure 9.12

Figure 9.12 Myosin head ADP (high-energy configuration) Pi 1 ATP Pi Myosin head (high-energy configuration) Myosin head attaches to the actin myofilament, forming a cross bridge. 1 2 Inorganic phosphate (Pi) generated in the previous contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. Figure 9.12

Figure 9.12 ATP ADP Pi Myosin head (high-energy configuration) Myosin head attaches to the actin myofilament, forming a cross bridge. (low-energy As new ATP attaches to the myosin head, the link between myosin and actin weakens, and the cross bridge detaches. 1 2 3 Inorganic phosphate (Pi) generated in the previous contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. Figure 9.12

Figure 9.12 ATP ADP hydrolysis Pi Myosin head (high-energy configuration) Myosin head attaches to the actin myofilament, forming a cross bridge. Thin filament As ATP is split into ADP and Pi, the myosin head is energized (cocked into the high-energy conformation). Inorganic phosphate (Pi) generated in the previous contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. (low-energy As new ATP attaches to the myosin head, the link between myosin and actin weakens, and the cross bridge detaches. Thick filament 1 4 2 3 Figure 9.12

Figure 9.12 ATP ADP hydrolysis Pi Myosin head (high-energy configuration) Myosin head attaches to the actin myofilament, forming a cross bridge. Thin filament As ATP is split into ADP and Pi, the myosin head is energized (cocked into the high-energy conformation). Inorganic phosphate (Pi) generated in the previous contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. (low-energy As new ATP attaches to the myosin head, the link between myosin and actin weakens, and the cross bridge detaches. Thick filament 1 4 2 3 Figure 9.12

Contraction of Skeletal Muscle Fibers Contraction – refers to the activation of myosin’s cross bridges (force-generating sites) Shortening occurs when the tension generated by the cross bridge exceeds forces opposing shortening Contraction ends when cross bridges become inactive, the tension generated declines, and relaxation is induced

Overview – Contraction of a Skeletal Muscle Principles of muscle mechanics: Force exerted by a contracting muscle on an object is muscle tension. Opposing force on the muscle by the weight of the object is called the load. A contracting muscle does not always shorten and move the load. Isometric vs. Isotonic A muscle contracts with varying force and for different periods of time in response to stimuli

The Motor Unit Each muscle is served by at least one motor nerve Contains axons of up to hundreds of motor neurons.

A motor unit = motor neuron and all the muscle fibers it supplies. The Motor Unit A motor unit = motor neuron and all the muscle fibers it supplies. Motor neuron fires - all of the fibers it innervates contract May have as many as several hundred or as few as four Fine control vs. gross (large) movements Muscle fibers are spread out within a unit Stimulation of a single motor unit causes a weak contraction of the entire muscle.

The Muscle Twitch Muscle twitch = the response of the motor unit to a single action potential The muscle fibers contract quickly and then relax Latent: excitation-contraction coupling is occurring Contraction: cross bridges are active Relaxation: initiated by reentry of Ca2+ into the SR

Developmental Aspects All muscle tissues develop from embryonic mesoderm cells called myoblasts Skeletal muscle myoblasts fuse (multiple nuclei) Cardiac and Smooth develop gap junctions Smooth muscle has good ability to regenerate throughout life Muscle mass differs between sexes due to testosterone Muscle is highly vascularized – resistant to infection