MED310A Muscle 2_GPearcey PDF

Skeletal, Smooth Muscle and Cardiac Muscle Physiology 2: Anatomy, physiology, pharmacology and mechanisms of muscle contraction. Gregory Pearcey (Assistant Professor) School of Human Kinetics and Recreation [email protected]  Types of Muscle...

Skeletal, Smooth Muscle and Cardiac Muscle Physiology 2: Anatomy, physiology, pharmacology and mechanisms of muscle contraction. Gregory Pearcey (Assistant Professor) School of Human Kinetics and Recreation [email protected]  Types of Muscle Connected to Bones Present in Sphincters Voluntary motor controlled Striated Present within Heart Involuntary spontaneous + Present in Visceral Organs autonomic control Blood Vessels Eye (vision accommodation) Piloerector Non-striated  Smooth and Cardiac Muscle Share some features with skeletal muscle but have some unique characteristics  Multiunit Smooth Muscle Some shared properties between multiunit smooth muscle and skeletal muscle Neurogenic Consists of discrete units that function independently of one another Units must be separately stimulated by nerves to contract.  Multiunit Smooth Muscle (examples) Found in various locations throughout the body – In walls of large blood vessels – In large airways to lungs – In muscle of eye that adjusts lens for near or far vision – In iris of eye – At base of hair follicles  Single-Unit Smooth Muscle Cells and Functional Syncytia Most smooth muscle is single-unit smooth muscle, alternatively called visceral smooth muscle, because it is found in the walls of the hollow organs or viscera. – The muscle fibres that make up this type of muscle become excited and contract as a single unit. – A group of interconnected muscle cells that function electrically and mechanically as a unit is known as a functional syncytium.  Multiunit verses Unitary Smooth Muscle Multiunit SM cells are not electrically connected with gap junctions. SM cell Unitary SM cells are electrically connected depolarization or hyperpolarization can with gap junctions. SM cell depolarization or not spread from cell to cell via gap hyperpolarization can spread from cell to cell junctions. Contract or relaxation is isolated via gap junctions. Contract or relaxation is solely to the cell being stimulated. synchronized across many cells. *similar to skeletal muscle where each *similar to cardiac muscle where muscle cell contracts individually in depolarization is spread from cell to cell response to nerve stimulation  Smooth Muscle Cells: Small and Unstriated Found in walls of hollow organs and tubes No striations – Filaments do not form myofibrils – Not arranged in sarcomere pattern found in skeletal muscle Spindle-shaped cells with single nucleus Cells usually arranged in sheets within muscle Have dense bodies containing same protein found in Z lines  Smooth Muscle Smooth muscle (SM) differs from cardiac and skeletal muscle: 1) SM is not striated 2) SM contains dense bodies throughout the cytoplasm and plasma membrane Similar to Z-lines in skeletal muscle – act as attachment points for thin actin filaments which then overlap thick myosin filaments 3) The dense bodies, actin, myosin network is connected to a cytoskeletal network of non- contracting intermediate filaments which “like a house frame” connect the system to the plasma membrane 4) SM contracts via a sliding filament mechanism causing the SM cell to shorten and the widen like skeletal and cardiac muscle  Smooth Muscle Cells: contractile elements Three types of filaments – Thick myosin filaments: longer than those in skeletal muscle – Thin actin filaments: contain tropomyosin but lack troponin – Filaments of intermediate size: do not directly participate in contraction Form part of the cytoskeletal framework that supports cell shape Smooth Muscle Schematic Representation of the Arrangement of Thick and Thin Filaments in a Smooth Muscle Cell in Contracted and Relaxed States (Myosin)  Smooth Muscle Cells and Calcium The thin filaments of smooth muscle cells do not contain troponin, and tropomyosin does not block actin’s cross-bridge binding sites. Light-weight chains of proteins are attached to the heads of myosin molecules to form cross bridges.  The activation of smooth muscle (SM) actin/myosin cross bridging in response to an elevation in intracellular Ca2+ SM has no troponin Ca2+ binds to calmodulin forming a complex that activates an enzyme MLCK (myosin light chain kinase) within SM MLCK phosphorylates myosin, activating myosin ATPase activity which initiates myosin cross bridging with actin to produce contraction Skeletal and cardiac muscle, Ca2+ binds to troponin freeing myosin binding sites on actin, allowing actin to interact with myosin to produce contraction. Voltage gated Ca2+ channel  Comparison of the Role of Calcium in Bringing about Contraction in Smooth Muscle and Skeletal Muscle 17 Single-Unit Smooth Muscle: Myogenic Self-excitable (does not require nervous stimulation for contraction) Also called visceral smooth muscle Fibres become excited and contract as single unit Cells electrically linked by gap junctions Single-Unit Smooth Muscle: Myogenic Can also be described as a functional syncytium Contraction is slow and energy-efficient. – Well-suited for forming walls of distensible, hollow organs  Pacemaker Potential Membrane potential gradually depolarizes on its own due to shifts in passive ionic fluxes When membrane depolarizes to threshold, action potential is generated Repolarizes only to depolarize again; self- generating action potentials  Slow-Wave Potentials Gradually alternating hyperpolarizing and depolarizing swings in potential Caused by automatic cyclic changes in the rate at which sodium ions are actively transported across the membrane Self-Generated Electrical Activity in Smooth Muscle  Smooth Muscle is only Innervated by the Autonomic Nervous System Autonomic Nerve Axon - either sympathetic or Smooth muscle (SM) is innervated by the parasympathetic sympathetic and or parasympathetic nerves – the two arms of the autonomic nervous system. 1. When the autonomic nerves reach SM the axon divides into multiple axons to form a fish-net like plexus that surrounds the SM. 2. The axons of the plexus form structures called varicosities. Varicosities are the sites of transmitter release. 3. There are multiple varicosities along each axon. One action potential moving along an axon can stimulate the release of transmitter from multiple varicosities. The system act as a “sprinkler system” which sprinkles transmitter axon plexus (norepinephrine or acetylcholine ) on to the SM. 4. Varicosities don’t form distinct motor junctions A. The sympathetic nerves primarily release (as in skeletal muscle). A single SM cell can noradrenaline as a transmitter. receive transmitter from multiple varicosities B. The parasympathetic nerves primarily including varicosities from the sympathetic and release acetylcholine as a transmitter parasympathetic nerves.  Autonomic nervous system (ANS) stimulation can produce contraction or relaxation of smooth muscle (SM ). same transmitter can produce opposite responses (contraction vs relaxation). Each major transmitter – noradrenaline released by sympathetic nerves and acetylcholine by parasympathetic nerves can contract or relax SM. The type of response you get (contraction vs relaxation) within a smooth muscle tissue will depend on: 1. The type and predominance of ANS innervation. Sympathetic vs Parasympathetic. 2. The predominance and subtype of receptor which is being stimulated by noradrenaline or acetylcholine. 3. The ability of the transmitter to access a given receptor.  An example of a Unitary Smooth Muscle Cell (SMC) tissue – the Gut Parasympathetic Nerves & Acetylcholine increase slow wave (SW) frequency, peristalsis and SMC contraction via M 3 receptors. Sympathetic Nerves & Noradrenaline reduce SW frequency, peristalsis, and relax the SMCs via β receptors The stomach and intestines are composed of smooth muscle cells (SMCs) that are connected with gap junctions that allow the transmission of depolarization Peristalsis from cell to cell. Imbedded between the SMCs, and connected to the SMCs via gap junctions, are non-SMC pacemaker cells (Interstitial Cells of Cajal, ICC). ICC produce “slow waves“ of depolarization that are transmitted to the SMCs. The slow waves initiate Ca+2 action potential formation within the SMCs causing co- ordinated phasic contraction resulting in peristalsis that moves food through the gut. The system is electromechanically coupled.  Cardiac Muscle Found only in walls of heart Striated Cells interconnected by gap junctions Fibres are joined in branching network Innervated by autonomic nervous system  Cardiac Muscle Cardiac muscle is very similar to skeletal muscle with some important differences. Sarcomere structure is similar to skeletal muscle The mechanism of contraction is identical Cardiac Sarcomere What is different (from skeletal muscle). 1. The heart is spontaneously active no direct motor nerve connection to the CNS Heart contraction is initiated by pacemaker cells that produce action potentials in the Sino Atrial (SA) Node 2. Action potentials are transmitted between cardiac cells through gap junctions 1. intercalated discs form special “tunnels” between cells 2. Skeletal muscle cells are electrically isolated from each other Skeletal vs Cardiac Muscle Skeletal Muscle Cardiac Muscle Blood O2 Extraction at rest When compared to skeletal muscle, cardiac muscle has: 1. 20 X the volume fraction of mitochondria 2. 7.5 X the capillary density supplying blood 3. Extracts more O 2 from the blood 4. Has a high myoglobin content 5. Almost exclusively depends on oxidative Skeletal Cardiac phosphorylation (as apposed to glycolysis) for energy Muscle production These are characteristics of the ultimate slow twitch muscle fiber, yet paradoxically its twitch characteristics resemble the ultimate fast twitch muscle. Cardiac Cycle – synchronized sequential cardiac muscle contraction and relaxation 1. atrial + ventricular filling atrial contraction ventricular contraction Atria Pause A. B. C. Ventricles 1. In order to pump blood into the lungs and out into the body the cardiac muscle present in the atria and ventricles has to contract and relax in a sequential coordinated manner. A. The atria and ventricles fill when the heart is relaxed. B. The atria contract forcing more blood into the ventricles. C. After a delay the the ventricles contract simultaneously pushing blood into the lungs and body Modified cardiac cells form a conduction system that starts in the SA node and propagates action potentials (APs) to the atria then to the ventricles initiating contraction in the cardiac muscle cells within both areas. The SA node is the heart’s “Pacemaker.” SA node cells produce spontaneous, repetitive, unique, Ca2+ (not Na+) driven APs. ① The cells start at a resting membrane potential of - 60 mV. They are leaky to Na+ and Ca2+. The influx of Na+ and Ca2+ slowly depolarize the cells. ② When the Na+ and Ca2+ leak depolarize the cell to a threshold of -40 mV an AP is produced via a fast ③ influx of Ca2+ which plateaus at 0 mV. ② ③ Depolarization to 0 mV triggers a rapid efflux of ② K+ which hyperpolarizes the cells back to -60 mV. ③ ① ② ③ Repeat about 70 times per minute – the ① average resting heart rate in humans ①  Action potentials generated in the SA node spread through the conduction system and depolarize atrial and ventricular cardiac muscle cells causing them to evoke APs and contract 1. All cardiac muscle cells are electrically connected to each other through gap junctions present within intercalated discs. Gap junctions are protein tunnels that connect the cytoplasm of adjacent cells and transmit depolarization. 2. Every cardiac muscle cell can evoke an AP when it is depolarized to threshold. The cells within the conducting system can’t contract but they transmit depolarization to the cells in the atria and ventricles, which can contract, causing Every cardiac cell is connected electrically via the cells to produce APs and contract. gap junctions present within intercalated discs Depolarization spreads from cell to cell through gap junctions causing adjacent cells to fire action potentials depolarization  Sequence of Depolarization and Subsequent Contraction in the Heart Atria and ventricles are electrically insulated. Conduction between these areas only occurs through the conduction pathway. electrical barrier A. SA node B. The spread of C. There is a delay (.13s), D. Depolarization and spontaneously fires APs, depolarization and then depolarization and AP spread from the depolarization spreads production of APs APs are transmitted bottom (apex) up through the atria through the atria is down the conducting through the ventricle producing APs in the followed by atrial system to the apex of the cardiac cells, producing atrial muscle cells contraction (which ventricle. contraction, squeezing pushes blood into blood out into the the ventricles). lungs and body Excitation contraction coupling in cardiac vs skeletal muscle cells The mechanisms in the blue dotted The mechanisms in the red dotted boxes are the same in skeletal vs boxes are different in skeletal vs cardiac muscle cardiac muscle  ______ Action Potential – plasma membrane DHP receptor +++++ In Skeletal Muscle Cells The action potential travels T-Tubule SR through the T-tubule system and Ca2+ activates DHP-dihydropyradine receptor Ca2+ mechanical release of Ca2+ Voltage gated Ca2+ channels Ca2+ ______ Action Potential – plasma membrane T-Tubule + In Cardiac Muscle Cells Ca2+ The action potential travels Ca2+ through the plasma membrane SR and T-tubule system and opens Ca2+ voltage gated Ca2+ channels. Ca2+ voltage gated release of Ca2+ Autonomic Nervous System (ANS) Control of Heart Rate and Strength of Contraction Acetylcholine through The Autonomic Nervous System controls muscarinic receptor the heart rate and strength of ventricle (M2) stimulation contraction. The sympathetic (fight or flight) nervous system releases noradrenaline (NA) and adrenaline (AD) and bind to β1 receptors 1. depolarize the SA node cells causing them to beat faster (increasing heart rate) 2. enhance Ca2+ release which increases the force of ventricle cell contraction (forcing more blood from the ventricles). noradrenaline & adrenaline via β1 receptor stimulation The parasympathetic nervous system releases acetylcholine which binds to muscarinic (M2) receptors 1. hyperpolarizes the SA cells and reduces SA node firing and conduction slowing heart rate.  Intrinsic Control of Ventricular Contraction - “Starlings Law” When the heart ventricles fill with blood, the cardiac cells stretch. Stretching the cardiac cells produces a more optimal orientation of actin and myosin allowing a greater contractile force to be generated. Force of Ventricular Cell Contraction In a normal heart the more blood pushed into the heart (within normal limits), the greater the contractility of the heart cells and the larger ejection fraction of blood pumped out of the heart. This phenomena is termed “Starlings Law of the Heart” Ventricular Filling with Blood / Cardiac Muscle Stretch