Chapter 9 Part 2: The Physiology of Muscle Contraction PDF

Chapter 9 Part 2 The Physiology of Muscle Contraction Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Contraction – Background and Overview You decide to pick up a book. The decision-making activates the upper motor neurons in the brain to p...

Chapter 9 Part 2 The Physiology of Muscle Contraction Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Contraction – Background and Overview You decide to pick up a book. The decision-making activates the upper motor neurons in the brain to plan, initiate, and coordinate this movement. These neurons then synapse with the spinal cord, and an efferent signal is transmitted to motor neurons that activate skeletal muscle fibers at the neuromuscular junction. https://content.byui.edu/ Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved  Excitable cells such as neurons and muscle cells can change their resting membrane potentials in response to stimuli. Electrical signals generated due to large changes in RMP are called action potentials (APs). APs spread across the muscle cell. In order to travel from cell to cell, these electrical signals are converted to chemical signals. Neurons use the neurotransmitter acetylcholine (ACh), to activate muscle cells to contract. Neurotransmitters open up specific ion channels on the muscle cells Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Ion Channels play a major role in changing of membrane potentials. Two classes of ion channels are: Chemically gated ion channels – opened by chemical messengers such as neurotransmitters (ACh binding to ACh receptors on muscle cells). Create local changes in membrane potential (small depolarization). Voltage-gated ion channels – open or close in response to local changes in membrane potential created by the chemically gated channels. APs are created by these channels. Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved  Anatomy of Motor Neurons and the Neuromuscular Junction (NMJ) – Skeletal muscles are stimulated by somatic motor neurons – A part of the peripheral nervous system, the somatic nervous system consists of nerves that go to the skin and muscles, and is involved in conscious activities. Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved  Anatomy of Motor Neurons and the Neuromuscular Junction (NMJ) – Axons (long, threadlike extensions of motor neurons) travel from central nervous system to skeletal muscle – Each axon divides into many branches as it enters muscle – Axon branches end on muscle fiber, forming the NMJ § Each muscle fiber has one NMJ with one motor neuron – NMJ is a synapse [a synapse is a junction between 2 nerve cells or a nerve and muscle fiber, with a tiny gap across which impulses pass]. Axon Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved  Overview of Skeletal Muscle Contraction Axon of a motor neuron NMJ Muscle fiber NMJ is the region where motor neuron contacts the skeletal muscle. Consists of multiple axon terminals and underlying junctional folds of the sarcolemma Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved The Neuromuscular Junction Axon terminal (end of axon) and muscle fiber are separated by gel-filled space called synaptic cleft Stored within axon terminals are membrane- bound synaptic vesicles containing neurotransmitter acetylcholine (ACh) Motor end plate The motor end plate is The specialized postsynaptic region of a formed by infoldings of muscle cell is called a motor end plate. The sarcolemma, called motor endplate is immediately across the junctional folds. They synaptic cleft from the presynaptic axon terminal. contain millions of ACh receptors Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved The Big Picture - Four steps must occur for skeletal muscle to contract: 1. Events at neuromuscular junction 2. Muscle fiber excitation 3. Excitation-contraction coupling 4. Cross bridge cycling Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Events at the Neuromuscular Junction Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved  When a Nerve Impulse Reaches an NMJ, Acetylcholine (ACh) is Released 1. Motor neuron fires an AP down its axon 2. Voltage-gated Ca2+ channels open 3. Ca2+ enters the axon terminal down its electrochemical gradient. 4. Ca2+ entry causes ACh to be released into the synaptic cleft by exocytosis Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved  ACh diffuses across the synaptic cleft and binds to receptors on the sarcolemma ACh binding opens ions channels in the receptors that allow simultaneous passage of Na+ into the muscle fiber and K+ out of the muscle fiber. More Na+ enters than K+ exit, producing a local change in the membrane potential (end plate potential) ACh effects are terminated by its breakdown in the synaptic cleft by acetylcholinesterase (enzyme) and diffusion away from junction. Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved A&P Flix: Events at the Neuromuscular Junction Click here to view ADA compliant Animation: Events at the Neuromuscular Junction https://mediaplayer.pearsoncmg.com/assets/apf-events-at-the-neuromuscular-junction Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Summary of events at the neuromuscular junction 1. AP arrives at axon terminal 2. Voltage-gated calcium channels open, calcium enters motor neuron 3. Calcium entry causes release of ACh neurotransmitter into synpatic cleft 4. ACh diffuses across to ACh receptors, opening chemical-gated Na+ channels on sarcolemma. Na+ entry causes local depolarization (end plate potential, EPP) 5. Acetylcholinesterase degrades ACh Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Clinical – Homeostatic Imbalance Many toxins, drugs, and diseases interfere with events at the NMJ – Example: myasthenia gravis: disease characterized by drooping upper eyelids, difficulty swallowing and talking, and generalized muscle weakness – Involves shortage of ACh receptors because person’s ACh receptors are attacked by own antibodies (autoimmune) Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Excitation – Generation of an Action Potential Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Generation of an Action Potential Across the Sarcolemma Resting sarcolemma is polarized, meaning a voltage exists across membrane – Inside of cell is negative compared to outside Action potential is caused by changes in electrical charges Occurs in three steps 1. Generation of end plate potential 2. Depolarization 3. Repolarization Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Generation of an Action Potential Across the Sarcolemma 1. End plate potential (EPP) – ACh released from motor neuron binds to ACh receptors on sarcolemma – Causes chemically gated ion channels (ligands) on sarcolemma to open – Na+ diffuses into muscle fiber § Some K+ diffuses outward, but not much – Because Na+ diffuses in, interior of sarcolemma becomes less negative (more positive) – Results in local depolarization called end plate potential Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved 2. Depolarization: – An Action Potential (AP) will only be generated if depolarization exceeds a certain threshold – If end plate potential causes enough change in membrane voltage to reach critical level called threshold, voltage-gated Na+ channels in membrane will open – Large influx of Na+ through channels into cell triggers AP that is unstoppable and will lead to muscle fiber contraction – AP spreads across sarcolemma from one voltage-gated Na+ channel to next one in adjacent areas, causing that area to depolarize Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Summary of Events in the Generation and Propagation of an Action Potential in a Skeletal Muscle Fiber Voltage-gated Na+ and K+ channels Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved 3. Repolarization: restoration of resting conditions (electrically) – Na+ voltage-gated channels close, and voltage-gated K+ channels open – K+ efflux out of cell rapidly brings cell back to initial resting membrane voltage – Refractory period: muscle fiber cannot be stimulated for a specific amount of time, until repolarization is complete – Ionic conditions of resting state are restored by Na+-K+ pump § Na+ that came into cell is pumped back out, and K+ that flowed outside is pumped back into cell Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Action Potential Tracing Indicates Changes in Na+ and K+ ion Channels Recording of an action potential (AP) in a muscle fiber. Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Excitation-Contraction (E-C) Coupling Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Excitation-Contraction (E-C) Coupling Excitation-contraction (E-C) coupling: events that transmit AP along sarcolemma (excitation) are coupled to sliding of myofilaments (contraction) AP is propagated along sarcolemma and down into T tubules, where voltage-sensitive proteins in tubules stimulate Ca2+ release from SR – Ca2+ release leads to contraction AP is brief and ends before contraction is seen Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Excitation-Contraction (E-C) Coupling is the Sequence of Events by Which Transmission of an Action Potential Along the Sarcolemma Leads to the Sliding of Myofilaments Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Transmission of the AP along the T- tubules of Triads causes voltage-sensitive tubule proteins to change shape. Shape change stimulates the interacting Ca2+ release channels in the terminal cisterns of the SR to release Ca2+ ions into the cytosol. Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved  Calcium binds to troponin; troponin changes shape, and removes blocking action of tropomyosin. Myosin- binding sites on the thin filaments are exposed. Myosin binding to actin forms cross bridges and contraction begins, concluding the E-C coupling. Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Contraction: EC-Coupling At low intracellular Ca2+ concentration: – Tropomyosin blocks active sites on actin – Myosin heads cannot attach to actin – Muscle fiber remains relaxed In response to AP, voltage-sensitive proteins in T tubules change shape, causing sarcoplasmic reticulum (SR) to release Ca2+ to cytosol At higher intracellular Ca2+ concentrations, 2 Ca2+ bind to troponin Troponin changes shape and moves tropomyosin away from myosin- binding sites Myosin heads is then allowed to bind to actin, forming cross bridge Cycling is initiated, causing sarcomere shortening and muscle contraction Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Contraction: EC-Coupling When nervous stimulation ends, the voltage sensitive tubule proteins return to their original shape, and the Ca2+ release channels of the SR close. Ca2+ in the sarcoplasm is actively pumped back into the SR by active transport. In the absence of Ca2+, the blocking action of tropomyosin is restored, myosin can no longer interact with actin, and relaxation occurs. The E-C sequence is repeated every time an AP arrives at the NMJ. Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved A&P Flix: Excitation-Contraction Coupling Click here to view ADA compliant Animation: Excitation-Contraction Coupling https://mediaplayer.pearsoncmg.com/assets/apf-excitation-contraction-coupling Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Contraction: Cross-Bridge Cycling Four steps of the cross bridge cycle: 1. Cross bridge formation: high-energy myosin head attaches to actin thin filament active site Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Contraction: Cross Bridge Cycling 2. Working (power) stroke: myosin head pivots and pulls thin filament toward M line M-line Z-line Z-line Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Contraction: Cross Bridge Cycling 3. Cross bridge detachment: ATP attaches to myosin head, causing cross bridge to detach Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Muscle Fiber Contraction: Cross Bridge Cycling 4. Cocking of myosin head: energy from hydrolysis of ATP “cocks” myosin head into pre-stroke high-energy position § This energy will be used for power stroke in next cross bridge cycle Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved The Cross Bridge Cycle Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved A&P Flix: Cross Bridge Cycle Click here to view ADA compliant Animation: Cross Bridge Cycle https://mediaplayer.pearsoncmg.com/assets/apf-cross-bridge-cycle Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved Clinical – Homeostatic Imbalance Rigor mortis – 3–4 hours after death, muscles begin to stiffen § Peak rigidity occurs about 12 hours postmortem – Intracellular calcium levels increase because extracellular Ca2+ comes into cell. § Results in cross bridge formation – Shortly after breathing cessation, ATP continues being consumed although no more is synthesized. § Cross bridge detachment impossible after all the ATP is depleted § Results in myosin head staying bound to actin, causing constant state of contraction – Muscles stay contracted until muscle proteins break down, causing myosin head to release Copyright © 2019, 2016, 2013 Pearson Education, Inc. All Rights Reserved