PHSL 3051 Muscle & Movement Lecture Notes Fall 2024 PDF

Muscle & Movement PHSL 3051 Dr. Barnett Skeletal Muscle: Excitation-Contraction Coupling Learning Objectives Class 11: Skeletal Muscle and Excitation Contraction Coupling Derrickson (1st edition: p. 364-381, 2nd edition: p 375- 392) 1. Draw and label a diagram that shows skeletal muscle at all a...

Muscle & Movement PHSL 3051 Dr. Barnett Skeletal Muscle: Excitation-Contraction Coupling Learning Objectives Class 11: Skeletal Muscle and Excitation Contraction Coupling Derrickson (1st edition: p. 364-381, 2nd edition: p 375- 392) 1. Draw and label a diagram that shows skeletal muscle at all anatomical levels 1. Muscle fascicles 2. Single muscle cells 3. Myofibrils and Sarcomeres. 4. At the sarcomere level your drawing should identify the molecular components that are the basis of its striated appearance. Include two different stages of myofilament overlap. 2. Draw the structure of the neuromuscular junction including important proteins that are found on the pre- and post-synaptic membranes (label these proteins and other structural features). 3. List in sequence the steps involved in neuromuscular transmission for skeletal muscle and point out the location of each step on a diagram of the neuromuscular junction; name the neurotransmitter and describe three ways the neurotransmitter molecules in the synaptic cleft are removed after the nerve stops sending signals. 4. List the steps in excitation-contraction coupling in skeletal muscle, and describe the roles of the sarcolemma, transverse tubules, sarcoplasmic reticulum and the thin and thick filaments. Be certain to include the roles of modulatory proteins such as troponin and tropomyosin and of calcium ions. 5. Diagram the chemical and mechanical steps in the cross-bridge cycle, and explain how the cross- bridge cycle results in shortening of the muscle. 6. Describe Ca2+ accumulation in the sarcoplasmic reticulum mediated by Ca-ATPase. Explain the role that these (Ca2+-ATPase pump proteins) transporters play in muscle function. 7. Name three (3) roles of ATP in skeletal muscle contraction and relaxation. 2  Contraction and Relaxation of Skeletal Muscle Fibers Topics for Today  Skeletal Muscle Excitation Review of Somatic Motor Neuron Stimulation of a Skeletal Muscle Fiber to Generate an Action Potential. Action Potential Triggering of SR Calcium Release  Skeletal Muscle Contraction Sliding Filament Mechanism. The Contraction Cycle  Excitation–Contraction Coupling in Skeletal Muscles.  Skeletal Muscle Relaxation 3  Skeletal Muscle Fibers are: A. Also known as fasicles B. The same as muscle cells C. Typically have a branched structure 4 The Neuromuscular Junction (NMJ) Synapse between a somatic motor neuron and a skeletal muscle fiber  Pre-synaptic terminal Neuronal axon terminal  Motor end plate Specialized region of the skeletal muscle membrane Post-synaptic side of the NMJ  End plate potential (EPP) Depolarization generated at the muscle membrane due to binding of the neurotransmitter Acetylcholine (ACh). Triggers an action potential if the EPP exceeds the threshold for voltage-gated sodium channels. 5  The Neuromuscular Junction LO 2 Somatic Motor Neuron Axon Plasma membrane of muscle fiber Synaptic vesicle containing Cytoplasm acetylcholine (ACh) Motor end plate Synaptic end bulb Synaptic cleft (space) Junctional fold Acetylcholine Acetylcholinesterase receptors The Neuromuscular Junction of a Skeletal Muscle Fiber 6  Excitation: Initiation of a Muscle Cell Action Potential 1 LO 3 Nerve Axon of somatic action motor neuron potential 2 2 Ca2+ Ca2+ Synaptic Voltage-gated end bulb Ca2+ channel Voltage-gated Na+ channel Plasma Na+ Ca2+ Cytoplasm Na+ Voltage-gated Synaptic Synaptic membrane vesicles Na+ channel cleft 3 Acetylcholinesterase Acetylcholine (AChE) (ACh) Nicotinic 8 Propagation of ACh 8 Propagation of action potential receptor Na+ action potential 7 Muscle action 7 Muscle action potential potential 6 Spread of 4 6 Spread of EPP to adjacent EPP to adjacent membrane K+ membrane Cytoplasm 5 End plate potential (EPP) Motor end plate 7 Muscle Action Potential 8  Membrane Components of Excitation– LO 4 Contraction Coupling  Triad: The junction of the Transverse Tubule with the Sarcoplasmic Reticulum  Dihydropyridine receptor (DHP or DHPR)  L-type voltage-gated Calcium channel family  Found in the T-tubule membrane  Moves in response to action potentials  Ryanodine receptor (RyR)  Calcium release channel  Found in the SR membrane Rest  Opens to release Ca2+when the DHP receptor moves  Sarcoplasmic Reticulum Calcium-ATPase  Other names  SR Ca2+-ATPase  Calcium Pump Protein  SERCA (Sarco- Endoplasmic Reticulum Calcium pump)  Found in the SR membrane  Pumps Ca2+ from the cytoplasm into the SR against its concentration gradient Active 9  Contraction of Skeletal Muscle Fibers Sliding Filament Mechanism LO 4 Myosin heads attach to the thin filaments and pull on them in both halves of the sarcomere The thin filaments slide inward and towards the center of the sarcomere The width of the A-band does not change The width of the I-band appears to narrow The individual lengths of the thick and thin filaments do not change Contraction results in the Z- discs coming closer together and sarcomere shortening occurs. Sarcomere shortening leads to  Myofibrils shortening which leads to Whole muscle shortening  10 Relaxed Muscle In the absence of Calcium (Ca2+) myosin can bind and hydrolyze ATP, generating ADP and phosphate (Pi). As myosin hydrolyzes ATP, the shape of the crossbridge domain (myosin head) changes. This is often represented in textbooks as a shift from a 45° conformation to a 90° conformation. The affinity of myosin for actin in this state is weak and no force can be produced because Tropomyosin is More recent time- blocking the myosin binding sites on resolved measurements the actin subunits of the thin filament. show myosin to be mobile before and after The idea of the 45° to 90° the hydrolysis of ATP. conformation comes from some fairly old electron microscopy data.  The Contraction Cycle LO 4, 5 & 7 Attachment to actin ATP hydrolysis Active Four major steps 1. ATP hydrolysis: myosin is “energized” and “perpendicular” to the thin filament. ADP and phosphate are still attached. 2. Attachment of myosin to actin: myosin head attached to the binding site on actin. The Detachment of myosin from actin phosphate group is released. This is a Crossbridge. Power stroke 3. Power stroke: myosin head pivots Phosphate ion and pulls the thin filament toward the center of the sarcomere. This generates force. ADP is released. 4. Detachment of myosin from actin: Crossbridge remains attached to actin until it binds another ATP – then myosin heads detach. 12  Excitation–Contraction Coupling LO 4 ,6 & 7 Relaxed Muscle 13  Excitation–Contraction Coupling LO 4 Contracting Muscle 14  Contraction Summary LO 2 – 7 15 During E-C Coupling DHP Receptors: A. Open and depolarize the T-tubules B. Open for Ca2+ flow down its concentration gradient C. Open the SR’s RyR receptor channels 16  Three Roles of ATP in Skeletal Muscle Contraction and Relaxation LO 7 1. Provides energy for force production during muscle contraction via ATP hydrolysis. 2. Releases myosin from actin at the end of the power stroke by binding to the myosin ATPase site. 3. Provides energy to pump calcium from the sarcoplasm (cytoplasm) into the sarcoplasmic reticulum during muscle contraction to cause muscle relaxation. 17