Summary

This document provides an introduction to muscle types and structure. It covers skeletal, smooth, and cardiac muscle tissues and their respective roles in the human body. The document also touches on the concepts of muscle contraction and relaxation.

Full Transcript

# Introduction to Muscle ## Introduction - **Question:** What is a muscle? - **Answer:** Tissue specialized to convert biochemical reactions into mechanical work. ## Muscle Function - Two main functions are to generate: - **Contraction** - **Expansion** - except when physically pulled by...

# Introduction to Muscle ## Introduction - **Question:** What is a muscle? - **Answer:** Tissue specialized to convert biochemical reactions into mechanical work. ## Muscle Function - Two main functions are to generate: - **Contraction** - **Expansion** - except when physically pulled by antagonistic muscle groups - Also generate heat & contribute to body temperature homeostasis. ## Muscle Types - Three types of muscle in the human body: - **Skeletal** - Attached to bones of the skeleton - Contract in response to a signal from a somatic motor neuron - Cannot initiate contraction on its own or be influenced by hormones - **Smooth** - Primary muscle of internal organs and tubes (e.g., stomach, blood vessels, urinary bladder) - Influences the movement of materials through the body. - **Cardiac** - Found only in the heart - Pump to move blood around the body - We will mainly focus on skeletal muscle in this unit. ## Gross Structure of Skeletal Muscle ### Characteristics - Responsible for positioning and movement of the skeleton - Skeletal muscles make up ~40% of body weight ### Structure - Outer connective tissue → **epimysium** - Contains bundles of muscle tissue called **fascicles** - Fascicles are covered by the **perimysium** → a connective tissue sheath - Nerves and blood vessels - Muscle fibers (muscle cells) are found within each fascicle - Covered by an innermost connective tissue sheath → **endomysium** - Within the muscle fibers are the functional units of skeletal muscle → **myofibrils** - Contain so many myofibrils that there is little room for other organelles - Cytosol contains many glycogen granules (energy storage) & mitochondria (ATP synthesis) ## Structure of a Muscle Fibre - Long, cylindrical cell - Several hundred nuclei on the surface of the fiber - Cell membrane is called the **sarcolemma** - Majority of the space is taken up by the **myofibrils** - Myofibrils are contractile and elastic protein bundles ## Organization of the Myofibril ### Characteristics - Myofibrils occupy most of the space in a muscle fiber - They are highly organized and consist of bundles of contractile elastic proteins. - **Contractile proteins** → actin & myosin - **Regulatory proteins** → troponin & tropomyosin - **Accessory proteins** → nebulin (aligns thin filament) & *titin* (elastic protein that returns stretched muscle to its relaxed state) ### Contractile Proteins - **Myosin** - A motor protein that consists of two coiled protein molecules (chains) that have two important parts → head & tail region - These two regions are joined by a flexible hinge - About 250 myosin molecules join - Arranged so that the heads are at the ends and the tails are together - **Actin** - Subunits G-actin (globular actin) - The G-actin subunits polymerize to form chains (F-actin) - Two F-actin chains twist together - this forms the basis of the thin filament - The coiled F-actin associates with regulatory proteins → *troponin* and *tropomyosin* - These proteins regulate muscle contraction. - Forms the completed thin filament. ## The Sarcomere - When observed under the light microscope, the myofibrils have stripes called striations (skeletal muscle = striated muscle) - The stripes were given names before anyone knew what they were for. - One repeated pattern of this unit forms a **sarcomere** - A sarcomere is made up of organized thick and thin filaments that results in the striations seen in skeletal muscle. - **Z-Line (disks)** → this is the site of attachment for thin filaments - One sarcomere is made of 2 Z discs & the filaments between them. - **I Band (isotropic)** → this is a region containing only thin filaments - A Z disc runs through the middle of an I band → thus each ½ of the I band is part of a different sarcomere. - **A Band (anisotropic)** → this is a region containing thick and thin filaments - The thick and thin filaments overlap at the outer edges of the A band. - **H Zone (part of the A band)** → this is a region containing only thick filaments. - The central region is lighter than the outer edges - **M Line** → this is a site of attachment for the thick filaments - The M line is the center of the sarcomere. ## Skeletal Muscle Contraction - Skeletal muscles only contract when stimulated by a signal from the nervous system. - Excitation-contraction coupling is the series of electrical and mechanical events in a muscle that leads to muscle contraction. - Occurs through an action potential in the muscle membrane → the EPPs are essentially always above threshold and cause muscle to contract. ### Contraction 1. **ACh** is released by the neuron into the synaptic cleft at the neuromuscular junction and binds to **nicotinic cholinergic receptors** on the motor end plate → the receptors are *Na+/K+ channels*. 2. The binding of **ACh** opens the channels → both *Na* & *K+* move across the membrane. - **ACh** is removed by *acetylcholinesterase*. - *Na+* influx exceeds *K+* efflux → local depolarization occurs at the synapse (called an *End Plate Potential - EPP*). 3. The **end plate potential** (action potential) then moves down the T-tubule system. - T-tubule membrane contains **dihydropyridine receptors (DHP receptors)** → L-type calcium channel - Depolarization changes the conformation of the DHP receptors. - DHP receptors are mechanically linked to the *Ca2+* channels of the *SR* known as *ryanodine receptors - RyR*. 4. **DHP receptor** then changes *RyR* conformation which results in the opening of *SR Ca2+* channels → *Ca2+* leaves the SR. - This increases cytosolic [Ca2+]. 5. *Ca2+* binds to **troponin** (a regulatory protein) on the thin filament → This shifts **tropomyosin** (another regulatory protein) into the "on" position revealing actin binding sites. 6. **Myosin** is now able to bind to actin and go through the cross bridge cycle. ## Crossbridge Cycle - **Myosin** is a motor protein capable of converting chemical energy (ATP) into movement. - Crossbridge cycling is easiest to understand when illustrated step-by-step: - **Step A:** Active site on *actin* is exposed when *Ca2+* binds to *troponin*. - **Step B:** Myosin head binds to *actin* at the actin binding site and forms a crossbridge. - **Step C:** The inorganic phosphate releases from *myosin* that causes the myosin head to pivot toward the center of the sarcomere (called the power stroke). - This pulls the thin filament towardsthe M line. - **Step D:** A new molecule of *ATP* attaches to the myosin head, causing the crossbridge to detach. - **Step E:** The myosin ATPase hydrolyses *ATP* → *ADP* + *P* which returns *myosin* to the cocked position. - Return to step B to continue the cycle if *Ca2+* is bound to *troponin*. - During contraction, the crossbridges do not all move simultaneously. - While some crossbridges are attached to *actin*, others are not. - At any one instance during contraction about 50% of the cross bridges are attached and produce contraction in the muscle. ## Skeletal Muscle Relaxation - Relaxation of skeletal muscle occurs when *Ca2+* is pumped back into the *SR* through the *Ca2+-ATPase*. - ↓ *Ca2+* in cytosol causes *troponin* & *Ca2+* to unbind. - The unbinding of *Ca2+* to *troponin* shifts *tropomyosin* into the "off" position and covers the binding sites on the actin subunits of the thin filament. - *Myosin* heads can no longer bind to the actin subunits. - Elastic elements pull filaments back to the relaxed position when *myosin* unbinds. ## ATP and Muscle Contraction ### Introduction - Muscles convert biochemical energy into mechanical work. - *Ca2+* controls muscle contractions → removed from the cytosol by *Ca2+-ATPase*. - *Na+* and *K+* ions are pumped back into/out of the cell using *ATP*. - *Myosin: Actin* interaction uses *ATP*. ### ATP - *ATP* is the main energy currency of the cell (*ATP* is a nucleotide triphosphate). - Muscle contraction requires a steady supply of *ATP*. - Energy is transferred from nutrients → - Occurs aerobically or anaerobically - *Glycolysis* occurs in the presence (aerobic) or absence (anaerobic) of oxygen. - Provides limited amount of *ATP*. - Generates unwanted metabolites in the absence of oxygen. - *Oxidative Metabolism* requires oxygen present (comes from the air you breathe) - Provides up to 15X more *ATP* per glucose molecule. - Does not produce toxic end products - Oxidative metabolism provides most of the energy required for muscle contraction when oxygen is available. ### Creatine Phosphate - Creatine phosphate is a high energy phosphate molecule. - Muscles have a high concentration of creatine phosphate. - Provides a rapid source of energy for the muscle. - Easily donates the inorganic phosphate to *ADP* to create *ATP* → provides a limited supply of *ATP*. - Used mainly to buffer [*ATP*] over very short time scales (i.e., seconds). - Reaction: creatine phosphate + *ADP* → *ATP* + creatine - Muscles contain large amounts of *CK*. - Resting muscles store energy in creatine phosphate ## Classification of Muscle Fibres - Two important terms relating to muscle contraction: - **Twitch** → single contraction-relaxation cycle - **Latent period** → short delay between the AP & the beginning of the muscle tension - Skeletal muscle is specialized for certain types of activity. - Functions are seen in morphological and biochemical adaptations in the muscle. - Three general types of muscle fibers: - **Slow-twitch fibers (type I)** - **Fast-twitch oxidative-glycolytic fibers (type IIA)** - **Fast-twitch glycolytic fibers (type IIX)** - Oxidative or glycolytic refer to the primary sources of ATP. - Oxidative fibers usually appear red due to the presence of *myoglobin*. - *Myoglobin* → an oxygen-carrying heme protein. - Oxidative fibers are smaller than glycolytic fibers, have numerous mitochondria & are better vascularized. - Fast or slow refers to the rate of *myosin* *ATPase* activity. - Fast fibers can split *ATP* more quickly and can contract/develop tension faster. - Result of the presence of different isoforms of *myosin*. - The length (duration) of contraction also varies between fibers. - Fast fibers have a shorter twitch (they can have more twitches per unit time) - Twitch duration is determined by the rate of removal of *Ca2+* from the cytosol. - Short twitch duration is useful for rapid, small muscle contractions (e.g. playing the piano, typing). - Long twitch duration good for long sustained movements (lifting heavy loads). - **Question:** Which type of muscle has the highest rate of *Ca2+* removal from the cytosol? ## Mechanics Of Muscle Contraction & Body Movement ### Muscle Contraction - **Resting Fibre Length** - The tension exerted by a muscle during a single twitch is influenced by: - The muscle type - Sarcomere length at the start of contraction - Sarcomere length is the degree of overlap between the thick and thin filaments. - **Too little overlap:** - Few crossbridges - Little force can be generated - **Too much overlap:** - Actin filaments start to interfere with each other. - Less force generated. - **Way too much overlap:** - Thick filaments collide with Z disk - Force rapidly decreases. ### Force Of Muscle Contraction - **NOTE:** A single twitch does not represent the maximum force the muscle fiber can develop. - Force of a muscle fiber can be increased increasing the rate of action potentials that stimulate the fiber. ### Summation - Increase in force generated by a muscle. - Due to repeated stimulation from action potentials that occur before the muscle has fully relaxed. ### Tetanus - Term for the state of a muscle when it reaches maximum force of contraction. - **Incomplete (unfused) tetanus:** - Slow stimulation rate → fiber relaxes slightly between stimuli - **Complete (fused) tetanus:** - Fast stimulation rate → fiber does not have time to relax ### Motor Unit - The motor unit is the basic unit of contraction in an intact skeletal muscle. - A muscle is made up of many different motor units. - A motor unit is composed of two components: - A group of muscle fibers - The somatic motor neuron that controls them. - All muscle fibers are of the same skeletal muscle fiber type. - An action potential in the somatic motor neuron → contraction of ALL muscle fibers in each motor unit. - Each motor unit contracts in an all-or-none fashion. ### Body Movement - Two main types of muscle contraction: - **Isotonic** - Creates force and moves a load. - The load is usually constant, and the muscle length changes. - **Isometric** - Creates force without movement. - Muscle length is constant. - The load is usually greater than the force that can be applied. - **Question:** How can an isometric contraction create force if there is no change in muscle length? - **Answer:** Even though sarcomeres shorten, muscle length stays constant because these elastic elements stretch to take up force until fully stretched. # Smooth Muscle ## Gross Structure of Smooth Muscle - **Where is Smooth Muscle Found in the Body?** - Walls of hollow organs & tubes → not attached to bones of skeleton - Some important smooth muscles → bladder sphincter, intestine, walls of blood vessels ## Arrangement of Smooth Muscle Cells - Smooth muscle can be arranged in two different ways: - **Single unit** → - Not necessary to electrically stimulate each individual fiber - Found on walls of internal organs → e.g., blood vessels - **Multi-unit** → - Each individual muscle fiber is separately innervated - e.g., iris of the eye, parts of reproductive organs ## Differences Between Smooth & Skeletal Muscle - **Whole muscle level:** - Contraction of smooth muscle changes muscle shape, not just length. - Smooth muscle develops tension (force) slowly. - Smooth muscle can maintain contraction longer without fatiguing → important because some are contracted most of the time (e.g.) - **Cellular level:** - Fibres much smaller in smooth muscle than skeletal muscle fibres. - About the same diameter as a single myofibril in a skeletal muscle fibre. - Actin & myosin are not arranged into sarcomeres - Thus, no banding pattern (no striations). - Actin & myosin arranged in long bundles diagonally around periphery of the cell. - Actin anchored at cell membrane structures called dense bodies - Not attached to the Z lines as in skeletal muscle - No T-tubules in sarcolemma, not much sarcoplasmic reticulum (SR) - Smooth muscle cells have special vesicles called *caveolae* that are invaginations of the sarcolemma that are specialized for cell signalling. - Force of contraction is related to the amount of *Ca2+* released. ## Smooth Muscle Contraction - **Role of *Ca2+* in Contraction** - Major difference between contraction of smooth muscle & cardiac muscle is the role of phosphorylation in regulating the smooth muscle contraction process. - Signal to initiate contraction is increase in cytosolic *Ca2+*. - *Ca2+* enters from extracellular fluid (ECF) through: - Voltage-gated channels → open when cell depolarizes - Stretch-activated channels → open when membrane stretched - Chemically-gated channels → open in response to hormones - *Ca2+* entry from the ECF results in the release of *SR Ca2+*. - *Ca2+* binds to *calmodulin (CaM)* in the cytosol. - *Ca2+/CaM* activates the enzyme *myosin light chain kinase (MLCK)* - *MLCK* activates *myosin* by phosphorylating the light chain of the *myosin* molecule in the head using energy and *P* from *ATP* → this *ATP* is used to activate the *myosin* through phosphorylation (not for crossbridge cycling) - When *myosin* is not phosphorylated, *ATPase* activity is blocked. - When *myosin* is phosphorylated, *ATPase* is active. - The phosphorylated myosin (active) can now interact with *actin* and go through crossbridge cycling and allow contraction to occur in the smooth muscle cell → remember, additional *ATP* is needed for each crossbridge cycle - *MLCK* uses the *P* from *ATP* to activate *myosin* (turn it "on"), but additional *ATP* is needed to go through crossbridge cycling for contraction to occur - *Note:* in smooth muscle the *myosin* is regulated → via phosphorylation of *myosin* - Whereas *actin* is regulated in skeletal muscle → via *troponin/tropomyosin* interaction with *actin*. - **Relaxation in Smooth Muscle** - Relaxation is a multi-step process: - *Ca2+* is removed from the cytosol - Pumped back into the SR using *ATP* to the extra-cellular environment through → - Decrease in *Ca2+* levels in the cytosol causes *Ca2+* to unbind from *calmodulin* → - *Myosin* light chains are dephosphorylated - Dephosphorylation of *myosin* does not automatically relax the muscle. - This allows the smooth muscle to enter the *latch state* → not fully understood. - Tension is maintained (*myosin* remains bound to *actin*) but with minimal *ATP* consumption. # Cardiac Muscle ## Gross Structure of Cardiac Muscle - Cardiac muscle cells are called **myocardial cells** → these are specialized muscle cells of the heart. - Shares features with both smooth and skeletal muscles - Most myocardial cells are typical striated muscle. - Contractile fibres organized into sarcomeres. - Cardiac muscle differs from skeletal muscle: - Cardiac muscle cells are much smaller with a single nucleus with about 1/3 of the cell volume is occupied by mitochondria. - T-tubules are much larger and branched and the sarcoplasmic reticulum (SR) is smaller. - Adjacent cells are joined by **intercalated discs** with desmosomes. - About 1% of cardiac muscle cells are *NOT* involved in contraction. - They are involved in the electrical excitation of the heart → known as the electrical conducting system of the heart. - They initiate heartbeat & allow the electrical excitation to spread rapidly throughout the heart. - They are connected to other cardiac cells via **gap junctions**. ## Cardiac Muscle Contraction - **Process of Contraction** - Like skeletal muscle contraction EXCEPT: - *Ca2+* enters through *Ca2+* channels on cell membrane as well as the SR. - *First: calcium enters through external* *Ca2+* *channels*. - *Next: calcium-induced calcium release* → *release of stored* *Ca2+* *from SR*. - *SR calcium provides about 90% of that* *needed* *for contraction*. - *Cardiac cells* have a *Na+/Ca2+* *antiport* (in addition to* *Ca2+-ATPase*). - *Removes* *Ca2+* *from cytosol and pumps it* *into the extracellular* *space*. - Exhibit **graded** (not all-or-none) contraction → the force generated x (is proportional to) number of active crossbridges. - Number of active crossbridges is proportional to cytosolic [*Ca2+*]. - Therefore, the force generated is proportional to cytosolic [Ca2+]. - **Factors Influencing Cardiac Muscle Contraction Force** - **Changes in [Ca2+]** - Regulated by epinephrine & norepinephrine → bind to & activate *ẞ1-adrenergic receptors*. - Binding then activates cAMP second messenger signaling pathway that leads to: - *a. Phosphorylation of voltage-gated* *Ca2+* *channels*: - *Increases the probability of the channel to open → increase* [*Ca2+* *] in the cytosol*. - *b. Phosphorylation of phospholamban*: - *Leads to increase* *SR Ca2+-ATPase* *activity → increase* *SR Ca2+*. - **Sarcomere length** - Tension generated length of muscle fibre. - Due to degree of overlap between actin and myosin→ - *Note that stretching a myocardial muscle cell may also allow more Ca2+to enter through cell membrane Ca2+channels → contributing to a more forceful next contraction*. ## Cardiac Muscle Contraction - Cardiac muscle is also an excitable tissue → can generate action potentials. - Major sequence of events: - **Phase 4:** Resting membrane potential. - **Phase 0:** Depolarization → The *AP* opens voltage-gated *Na* channels, causing a rapid increase in membrane *Na* permeability (close again). - **Phase 1:** Initial repolarization → open fast *K+* channels allow initial repolarization. - **Phase 2:** The plateau → initial depolarization triggered voltage-gated *Ca2+ channels* to slowly open, causing an increase in *Ca2+* permeability and the fast *K+* channels close. - **Phase 3:** Rapid repolarization → the *Ca2+* channels close and the slow voltage-gated *K+* channels open (initial depolarization was the trigger), and the resting stage ion permeability is restored (phase 4). - Result of sustained depolarization: - Typical action potential in neuron or skeletal muscle cell: 1-5 msec. - Typical action potential in cardiac muscle: >200msec - **Question:** Why is this important? - **Question:** Why don't cardiac muscle cells undergo summation and tetanus? - **Answer:** Because of the longer refractory period → means that the cell has finished contracting before the next action potential. ## Important Terms and Concepts ### Important Terms - Skeletal muscle - Cardiac muscle - Striated muscle - Muscle fibre - Myosin and actin - A band - I band - M line - Contraction - Sliding filament theory - Troponin - Excitation-contraction coupling - T-tubule - ACh - Acetylcholinesterase - Isotonic - Tetanus (complete and incomplete) - Fast twitch - Calcium-dependent calcium release - Smooth muscle - Tendon - Myofibril - Thick filament - Thin filament - Z line - H zone - Crossbridge - Relaxation - Myoglobin - Tropomyosin - Neuromuscular junction - EPP - Tension - SR - Load - Isometric - Summation - Phosphocreatine - Slow twitch - Dense bodies ### Important Concepts - Differences between skeletal muscle, smooth muscle, and cardiac muscle at whole muscle level, cellular level, and molecular level - Structure of the sarcomere - Sliding filament theory - Role of calcium - Excitation-contraction coupling - Role of *ATP* in muscle contraction. - Skeletal muscle fiber types - Tetanus, motor unit, and recruitment - Isotonic contraction and isometric contraction - Contraction mechanism in smooth muscle and cardiac muscle

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