Physiology of Skeletal and Smooth Muscle PDF

Smooth and skeletal muscle Where opportunity creates success  Types of muscle Skeletal – Attached to bones – Makes up 40% of body weight – Responsible for locomotion, facial expressions, posture, respiratory movements, other types of body movement – Vo...

Smooth and skeletal muscle Where opportunity creates success  Types of muscle Skeletal – Attached to bones – Makes up 40% of body weight – Responsible for locomotion, facial expressions, posture, respiratory movements, other types of body movement – Voluntary in action; controlled by somatic motor neurons Smooth – In the walls of hollow organs, blood vessels, eye, glands, uterus, skin – Some functions: propel urine, mix food in digestive tract, dilating/constricting pupils, regulating blood flow, – In some locations, autorhythmic – Controlled involuntarily by endocrine and autonomic nervous systems  Properties of muscles Excitability: capacity of muscle to respond to a stimulus Contractility: ability of a muscle to shorten and generate pulling force Extensibility: muscle can be stretched back to its original length Elasticity: ability of muscle to recoil to original resting length after stretched  Functions of the muscle system Body movement (Locomotion) Maintenance of posture Respiration – Diaphragm and intercostal contractions Communication (Verbal and Facial) Constriction of organs and vessels – Peristalsis of intestinal tract – Vasoconstriction of b.v. and other structures (pupils) Heartbeat Production of body heat (Thermogenesis) Skeletal muscle  Skeletal muscle structure Muscle fibers basic cellular unit, the sarcomere Muscle tissue is formed by bundles of fascicles fascicles are formed by bundles of muscle cells muscle cells are formed by bundles of myofibrils 1. Nuclei multiple, located in cell’s periphery 2. Sarcolemma tubular sheath that encases and defines each muscle fiber 3. T-tubules invaginations within the sarcolemma location for ion exchange. 4. Sarcoplasm – Sarcoplasmic reticulum – Mitochondria – Glycogen & ions – Myofibrils  Function of skeletal muscle Movement convert chemical energy into mechanical energy, thus generating force and power Body posture and position Store nutrients contributes to basal energy metabolism, serving as a storage site for essential substrates such as carbohydrates and amino acids Maintain body temperature produced by muscular activity  Myofibrils Actin – "thin fibers” – Double-helical structures – Polarised fibers Tropomysin- Troponin complex regulation of the interaction of actin with myosin heads Myosin – "thick fibers“ – light meromyosin anchor myosin at the M line – heavy meromyosin S-1 portion (myosin head) binds actin and contains an ATP // S-2 portion location power stroke Support proteins titin, desmin, myomesin, C protein, nebulin, and plectin  Sarcomere Structural and functional unit of actin:myosin–linked muscle contraction Are arranged longitudinally and include the M line, Z disk, H band, A band, and I band 1. Z disks terminal boundary of the sarcomere 2. I band terminal regions of two adjacent sarcomeres and contains only actin filaments 3. A band entirety of the myosin fibers and includes regions of actin and myosin overlap 4. H band M line and contains only myosin filaments Neuromuscular junction Where opportunity creates success  Motor neurons – are the nerves that innervate muscle fibers – anterior horns of the spinal cord Motor unit : single motor neuron and the muscle fibers it innervate Neuromuscular junction is the junction between Motor neuron and Skeletal muscle fiber. They are linked chemically. Neurotransmitter at neuromuscular junction is Acetylcholine. As axon approaches muscle , it divides into many terminal branches and loses its myelin sheath Axon terminal branch ends in a enlarged knob like structure called Terminal button. Vesicles which contain chemical transmitter are present in Motor end-plate A motor end plate is a chemical synapse between nerve terminals that invaginate into the surface of the muscle fiber 1. Axon Terminal - Contains around 300,000 vesicles which contain acetylcholine (Ach) 2. Synaptic Cleft : - 20 – 30 nm space between the axon terminal & the muscle cell membrane. 3. Synaptic Gutter ( Synaptic Trough) - It is the muscle cell membrane which is in contact with the nerve terminal. It has many folds called Subneural Clefts. Ach receptors are located here  Events at the neuromuscular junction 1. An action potential to the axon terminal (terminal button) 2. AP at the axon terminal causes the opening of Ca2+ channels 3. Ca2+ triggers the release of acetylcholine (ACh) 4. ACh diffuses across the synaptic cleft and binds with RECEPTORS on motor end plate 5. This binding causes opening of Na+ channels and Na+ entry into muscle cell 6. Na+ entry causes depolarization of Motor end plate called END PLATE POTENTIAL ( EPP) 7. The resultant Na+ entry initiates action- potential in the muscle fiber 8. Propagation of the action potential 9. Acetylcholine is destroyed by enzyme acetylcholinesterase  End plate potential Provoked by the influx of Na+ inside of the muscle fiber Local potential end plate It is the initiator of the AP Threshold  Action potential Skeletal muscle fibers No current flow deep within the fiber T tubule–sarcoplasmic reticulum system – Transmission of action potentials along transverse tubules – Transverse to the myofibrils – Open in the exterior of the fiber – Sarcoplasmic reticulum vesicular tubules high concentration of Ca+ T tubule action potentials release of Ca+ cause contraction This overall process is called excitation- contraction coupling  Release of Ca+ from the T tubule– sarcoplasmic reticulum system 1. Action potential 2. Dihydropyridine receptors feel voltage changes 3. Pull the ryanodine receptor channels out in the sarcoplasmic reticular cisternae 4. Ca+ release 5. Releasing causes contraction 6. Re-uptake of the calcium ions by a calcium pump by ATP  Cross-bridge cycle Interaction between the myosin heads (the cross-bridges) and the active site on the thin filaments 1. Muscle relaxed – Low free calcium ion concentration – Troponin–tropomyosin complex avoid the the cross-bridge 2. Muscle contracted – Increase intracellular calcium concentration – Calcium begin to bind to the Tn-C subunit associated with each tropomyosin molecule – Tropomyosin molecule to change its position – Interaction of myosin with actin  Cross-bridge cycle force generation and movement through the whole muscle fiber. 1. At rest – myosin heads in the thick filaments bound to ADP + Pi – Head 90° angle – No binding between myosin and action inhibitory action of tropomyosin 2. Binding actin and myosin tropomyosin removing 3. ADP and Pi removed 4. Head attached to the flexible S2 region pitches outward by 45° 5. Power stroke myosin head moves toward the negative end of actin displacing the actin filament and shortening the sarcomere 6. Detachment of myosin from actin ATP binds to the myosin head  Temporal summation One action potential = single contraction = Twitch Amount of force produced by a twitch very low TEMPORAL SUMMATION Enhance the contractile force generated by a muscle fiber stimulating a muscle fiber…. 1. at a time well past its electrical refractory period 2. at a time where it has not yet fully relaxed mechanically from a prior stimulus  partially fused twitches  tetanus Pathophysiology Where opportunity creates success Diseases of the neuromuscular junction Smooth muscle  Smooth muscle cell structure Cells are not striated Not arranged as symmetrically as in skeletal muscle Smaller than those in skeletal muscle and cylindrical shape 1. Nucleus single 2. Sarcolemma 3. Caveolae indentations in sarcolemma (may act like T tubules) 4. Myofilaments – Thick myosin (side-polar) – Thin similar to actin in skeletal muscle / lack the associated troponin protein complex – Intermediate cytoskeletal functions (noncontractile IF) 5. No sarcomeres 6. Dense bodies instead of Z disks – membrane-associated dense bodies (FA)anchors for thin  Grouped into sheets in walls of hollow organs – Longitudinal layer – muscle fibers run parallel to organ’s long axis – Circular layer – muscle fibers run around circumference of the organ Both layers participate in peristalsis  Functions of the smooth muscle Gastrointestinal tract - propulsion of the food bolus Cardiovascular - regulation of blood flow and pressure via vascular resistance Renal - regulation of urine flow Genital - contractions during pregnancy, propulsion of sperm Respiratory tract - regulation of bronchiole diameter Integument - raises hair with erector pili muscle Sensory - dilation and constriction of the pupil as well as changing lens shape  Cell-to-cell transmission of force and electrical activity Is innervated by autonomic nervous system (ANS) 1. Single-unit Is innervated by only one (or very few) nerve fibers per bundle Often autorhythmic More predominant in visceral rather than vascular smooth muscle 2. Multi-unit Each cell requires its own electrical impulse Arrector pili of skin and iris of eye  Properties single-units 1. Single-unit Gap junctions – Electrically coupled – GAP JUNCTIONS potential change is linked to contraction of the muscle cells spreading Innervation to few cells Produces slow, steady contractions to allow substances to move through the body, e.g. food in the GI tract Tone = level of contraction without stimulation Location walls of all visceral organs except the heart 2. Multi-unit No GAP junctions Innervation to each cell More precise muscle control Produces asynchronous contractions Location Large blood vessels, eyes and respiratory airways  Direct and Receptor–Mediated Factors that Contract or Relax Smooth Muscle Smooth muscle can be contracted or relaxed by dozens of chemical agents and physical stimuli Direct passive diffusion Receptor mediated binding of ligands to their specific membrane receptors  pharmacology treatments 1. Constrictors: Direct – Ca2+ binds to calmodulin activates myosin initiate cross-bridge attachment and cycling – O2  maintenance of contraction – Reactive oxygen species unknown mechanisms 2. Constrictors: Receptor mediated – Noradrenaline, adrenaline and dopamine α-adrenoceptors open plasma membrane calcium channels activation of PLC formation of IP3 and DAG release of calcium – Ach, serotonin, vasopressin, angiotensin II and ATP 3. Relaxants: Direct – NO Activation of guanylate cyclase cGMP, intracellular calcium removal – Hypoxia, CO2, cAMP and cGMP 4. Relaxants: Receptor mediated – Adrenaline β2-receptor  formation of cAMP. Important in bronchiole smooth muscle – Noradrenaline important in suppressing smooth muscle–mediated motility in the gut – Dopamine D1 receptors in renal vascular smooth muscle  Contraction smooth muscle Requires at least 1 μM increase in intracellular calcium concentration Calcium entry= Contraction / Calcium exit= relaxation 1. Direct entry – “leak” channels passive entry of small amounts normal conditions / pathological conditions (hypertension) large amount and excessive contraction – Voltage-gated calcium channels action potential (smaller amplitude and slower upstroke) – Ligand-gated calcium channels AP at higher concentrations (hormones and NTs) – Stretch-activated calcium channels 2. Via second messenger – IP3–induced release activation PLC formation IP3 IP3 binds to receptors on the SR release of calcium stored in the SR – Calcium-induced calcium release Intracellular calcium calcium release from the SR Stimulates IP3-induced release  Activation cross-bridge cycle smooth muscle lack the associated troponin protein complex Requires thick filament regulation  myosin- linked myosin molecule to start activation from a resting state 1. Increased intracellular calcium (via depolarization or hormone/neurotransmitter activation) but also…calcium-induced calcium release from the SR 2. Calmodulin binds calcium 3. Ca2+ -calmodulin complex activates myosin light-chain kinase (MLCK) 4. MLCK phosphorylates light chains in Myosin 5. Increase myosin ATPase activity  Smooth muscle relaxation Reduction cytoplasmic calcium concentration – repolarization and hyperpolarization / calcium pump and the sodium–calcium exchanger 1. Ca2+ decreases 2. Ca2+ unbinds from calmodulin 3. yosin light-chain phosphatase (MLCP)activity to dephosphorylates myosin 4. Dephosphorylated myosin has a low affinity for actin 5. Cross-bridge cycle interruption relaxation  Contractile activity in smooth muscle Cannot be divided clearly into twitch and tetanus Tonic contraction low level of active tension for long periods without cyclic contraction and relaxation ligand-gated calcium channels or by direct metabolic contractile factors Phasic contractions like a skeletal muscle twitch induced by momentary activation of voltage-gated calcium channels Pathophysiology Where opportunity creates success  Digestive system gastroparesis loss of motility – Nerve dysfunction, collagen disease, muscular dystrophies, amyloidosis, thyroid disease, diabetes mellitus, neuropathy… Renal system – Kidneys chronic kidney disease and can lead to end-stage renal disease – Ureters nephrolithiasis – Bladder neurogenic bladder disease Cardiovascular and respiratory system – Atherosclerosis, pulmonary hypertension, asthma Comparisons Among Skeletal, Smooth, and Cardiac Muscle