Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Smooth and Cardiac Muscle Lanny Shulman, O.D., Ph.D. University of Houston College of Optometry Smooth Muscle Found in: • Sheets lining walls of hollow viscera (i.e. gastrointestinal tract) • Attached to hair follicles • Blood Vessels Major Function: • Movement of viscera • Peristalsis • Vasoconstriction Distinguished from Other Muscle Tissues (Structural Differences): • Small spindle shaped fibers (2-5µm x 400 µm) • Single Nucleus • Lacks Cross-striations, Z Lines, myofibrils, sarcomeres • Dense Bodies • Actions are involuntary • Contain tropomyosin but no troponin • Poorly developed sarcoplamic reticulum Structural Differences cont.: • Gap Junctions between fibers • Intermediate Filaments (Desmin, Vimentin) • Few mitochondria—low ATP consumption • Relies mainly on aerobic glycolysis for metabolic needs • Caveolae Functional Differences: • Ca2+ ions trigger contractions through a different mechanism than that found in other muscle types. • Most Ca2+ ions that trigger contractions enter the cell from the extracellular fluid. • Cells are able to contract over a greater range of lengths than skeletal or cardiac muscle because actin and myosin filaments are not rigidly organized. Functional Differences cont.: • Autonomic innervation – Excitatory & inhibitory – Sympathetic & parasympathetic – Norepinephrine, Acetylcholine – No specialized endplate region – Multiple varicosities • Hormonal control • Automaticity Electrical Coupling • Single Unit – Found in walls of hollow organs (stomach, bladder, esophagus) – Contract rhythmically as spontaneous waves of contractions – Occur in large sheets – Low resistant bridges between individual cells—Gap Junctions – Function in a syncytial fashion – Has neuromuscular junctions that serve a bundle of muscle fibers – Slow; no AP Electrical Coupling • Multi-unit – Iris, large arteries, veins – Continuously active (sphincters, walls of blood vessels, sphincter and dilator muscles of eye) – Made up of individual units without connecting bridges-no Gap Junctions – Regulation of individual cells – Fine, graded contractions occur (eye) Contractile Responses • Tonic – Long forceful contraction – Constant Tone (latched)-no AP – BV walls, airways, many sphincters • Phasic – Typically not constricted – Intermittent forceful contractions-AP – GI, Urinary, Reproductive tissues, large arteries Calcium and Smooth Muscle • Regulates Cross-Bridge Cycling • Indirect role due to the absence of troponin • Ca2+ acts on the cross-bridge itself • Involves phosphorylation at a specific serine residue on the light chain • Uses ATP as a phosphate donor Calcium Mobilization • Phasic Contraction: 1. Single brief stimulus elicits transient increase in Ca2+ and small contraction (solid lines) 2. Repeated stimuli lead to transient increases and decreases in Ca2+ and summation of contractions (dotted lines). • Tonic Contractions: 1. Initial Ca2+ release from sarcoplamic reticulum induces rapid force development (solid lines). However, peak [Ca2+] is not maintained but remains above threshold until stimulus is removed. 2. If Ca2+ is blocked from SR (dashed lines), the contraction is much slower. Mechanisms Regulating Myoplasmic [Ca++] 1. Membrane potential-dependent Ca++ influx through Ca++ channels from extracellular space 2. Receptor-activated Ca++ channels in the sarcolemma 3. Control of Ca++ release from the sarcoplasmic reticulum 4. Sequestration and extrusion of Ca++ by pumps in both membranes 5. Na+- Ca++ exchange across the sarcolemma Molecular Basis of Contraction 1. 2. 3. 4. 5. 6. Intracelluar calcium levels rise to trigger contraction Ca2+ binds calmodulin (4:1). The active Ca2+-calmodulin-MLCK complex phosphorylates a serine residue on the myosin light chains associated with each myosin head. This phosphorylation requires one ATP. Fast cross-bridge cycling in smooth muscle. The release of ADP and Pi generates the power stroke. The conformation of the myosin head changes from 90o to 45o. This cycling requires a second ATP to bind the myosin head, to hydrolyze ATP to myosin-ADP-P, to release the myosin from actin, and reset the myosin head to a high potential energy 90o angle. Myosin light chain phosphatase is continually removing the phosphates put on myosin light chains by active MLCK. Model of the Latch State: • Special state that allows smooth muscle to maintain tone with minimal expenditure of ATP. • Myosin cross-bridges remain attached to actin after [Ca2+]i falls. • Produces sustained contraction with little expenditure of energy. Latch State Model cont. • If myosin light chains are dephosphorylated, ATPase activity decreases. • Myosin heads continue to hold force at muscle ends. • Low myosin ATPase activity probably exists even after dephosphorylation. Smooth Muscles of the Eye and Adnexa • Tarsal or Müller’s Muscle of the eyelid – Function: elevates upper lid, depresses lower lid – Innervation: sympathetic nervous system • Dilator muscle of the iris – Function: dilate the pupil (mydriasis) – Innervation: sympathetic nervous system • Sphincter muscle of the iris – Function: constrict the pupil (miosis) – Innervation: parasympathetic nervous system • Ciliary Muscle of the ciliary body – Function: accommodation (focus from distance to near) – Innervation: parasympathetic nervous system Cardiac Muscle • Found in the wall of the heart • Function is to pump blood to the body and maintain blood pressure • Cardiac cells are small with one central nucleus • Mechanism of contraction is similar to slow skeletal muscle • Cells are striated and joined end to end, forming fibers • Intercalated Discs & Gap Junctions • Cisternae are less well developed & store less Ca2+ than skeletal muscle • Extra Ca2+ is released from transverse tubules causing twitches to be 10x longer than skeletal muscle twitches • Energy needs are met by aerobic metabolism thus cells contain many mitochondria • Functions as a syncytium • Automaticity • Pacemaker cells Intercalated Discs • Gap Junctions • Desmosomes (maculae adherens) • Fasciae adherens Electrical Properties • In mammalian hearts, depolarization lasts ~ 2 ms. • Plateau phase and repolarization lasts 200 ms or more. • Repolarization is not complete until contraction is half over Phases of Action Potentials • Depolarization and overshoot are due to opening of voltage-gated Na+ channels (phase 0) . Na+ influx • The initial rapid repolarization (phase 1) is due to closure of the Na+ channels. No Na+ influx • The prolonged plateau is due to opening of voltage-gated Ca++ channels (phase 2). Ca++ influx • Repolarization to the resting potential (phase 3) is due to closure of the Ca++ channels and efflux of K+ through K+ channels. Ion Channels • Na+ channels: 2 gates; outer gate that opens at start of depolarization (-70 to -80 mV); inner gate that closes and stops influx of Na+ until AP is over. • Ca++ channels: activated at -30 to -40 mV • K+ channels: 3 types (1) ITO : early incomplete repolarization (2) IKr : at plateau potentials: allows K+ influx but resists K+ efflux (3) IKs : outward current; sum of IKr & IKs is small outward current that increases with time and repolarizes Mechanical Properties • Repolarization time decreases as cardiac rate increases. • Contractile response begins just after start of depolarization and lasts 1.5x as long as AP. • Skeletal muscle: release of [Ca2+]o due to depolarization • Cardiac muscle: release of [Ca2+]o due to activation of dihydropyridine channels • Absolute refractory period: Phases 0-2 and half of phase 3 ∴ tetanus is not possible Spontaneous Contraction Versus Neural Control 1. • • • 2. • • • • Purkinje Cells (cardiac conducting cells) Modified cardiac muscle cells Organized into nodes and bundles Transmit contractile impulse Unmylinated nerves Derived from vagus nerve (CN X) End near the nodes Do not initiate contraction Modify the rate of muscle contraction Injury and Repair • Mature cardiac cells do not divide • Injured cardiac muscle tissue is repaired by the formation of fibrous connective tissue • Loss of cardiac function at site of injury • This is pattern of injury and repair in non-fatal myocardial infarction