Excitation-Contraction Coupling Claudia Stanescu, Ph.D. Office Hours in Gittings 108 Tue 10-11am and Thurs 1-2pm or by appointmentObjectives: 1. Diagram and label the key components of the neuromuscular junction. 2. List in order the events that occur at the neuromuscular junction leading to the electrical stimulation of a skeletal muscle fiber. 3. Describe the role of AChE in the cessation of the electrical stimulation of a muscle fiber4. Discuss the role of calcium in the regulation of contraction and relaxation of skeletal muscle. Explain how calcium provides the link between the electrical activation of muscle fibers and initiation of the contraction cycle. 5. List in order the events of the contraction cycle. Be able to link these events with the excitation of the muscle fiber. Objectives:Terminology • Excitation: electrical signal is transmitted from a motor neuron to the muscle fiber • Excitation-Contraction Coupling: the events that connect excitation to contraction • Contraction: the events that cause the sarcomere and the muscle fiber to shorten • Relaxation: the events that cause the sarcomere and the muscle fiber to return to resting lengthSequence of Events 1. Electrical signal transmitted from a motor neuron to a skeletal muscle fiber (Excitation) 2. Triggers release of Ca2+ from SR (EC Coupling) 3. Ca2+ binds to troponin on the thin filament, thereby permitting crossbridges to form crossbridge cycling results in tension development (Contraction) 4. Removal of Ca2+ (resequestration into SR) results in Relaxation cell in nervous systemcell in muscle systemsarcoplasm reticulum TextThe ‘Electrical Signal’ - Excitation Neuromuscular Transmission 1. Activation of skeletal muscle is voluntary requires a signal from the central nervous system (CNS) this ‘signal’ results in an electrical impulse along a motor neuron, that arrives at the Neuromuscular Junction between nervous system and muscular system -spinal cord injuries cannot control legs because signals come from brain and cannot exit to muscles -muscles REQUIRE electrical signal from brains-electrical signal = action potential (where theymeet)Ch 12 - don’t have to know all details motorneuron comesfrom specific part of braintravels to spinal cordsynapses/connectsto another neurontransfers to handmotorneuronStructural Organization of Skeletal Muscle forms connection-voltage dataCa channels open-allows Ca toenter motor neuron-causes themto undergoexocytosis-acetylcholine =specific neuron-nerve impulse = change in voltage-> generates actionpotential (initiatedby sodium)-ACh doesn’t entercellNeuromuscular Junction (Excitation) Steps: 1) Action potential arrives at the synaptic end bulb of motor neuron and causes opening of voltage gated Ca2+ channels 2) Synaptic vesicles containing the neurotransmitter, Acetylcholine (ACh) undergo exocytosis 3) ACh is released into the synaptic cleft and binds to ACh receptors on the sarcolemma (motor end plate) 4) ACh receptors open and allow Na+ to enter the muscle fiber, generating an action potential on the sarcolemma 5) ACh is quickly broken down to Acetate and Choline by Acetylcholine Esterase (AChE)Neuromuscular junction animation • Neuromuscular Junction (captioned): http://www.youtube.com/watch?v=JcUwsFpxrbURelease of Ca2+ from the SR Excitation – Contraction Coupling 1. AP runs along sarcolemma, continues into T-tubules 2. Triggers release of Ca2+ from SR 3. Ca2+ diffuses into sarcoplasm and myofibrils 4. Ca2+ binds to troponin on thin filament myosin binding site on actin gets exposed 5. Crossbridges form  tension is generated (starts contraction)Excitation contraction coupling animation • Excitation Contraction Coupling (captioned): http://www.youtube.com/watch?v=a-nt19jZvnI •Relaxation - Sequestration of Ca2+ 1. When APs stop arriving at the NMJ, the ‘trigger’ to release Ca2+ from the SR stops 2. Active Ca2+ transporters in the SR membrane pump Ca2+ back into the SR 3. Cytoplasmic [Ca2+] decreases 4. As [Ca2+]cyto falls, Ca2+ comes off troponin - the myosin binding sites on actin get covered by tropomyosin 5. Crossbridge cycling stops and tension drops 6. Titin brings the sarcomere back to resting position -ATP transports Ca across gradientReview events: http://www.blackwellpublishing.com/matthews/myosin.html !!!!!!!! KNOW