MD137 Smooth Muscle Lecture PDF

Physiology School of Medicine 2024 Smooth Muscle MD137: Principles of Lecturer: Dr K.McCullagh Physiology CLASSIFICATION OF THE TYPES OF MUSCLES (Somatic Nervous System) (Autonomic Nervous System, ANS) The three types of muscles ...

Physiology School of Medicine 2024 Smooth Muscle MD137: Principles of Lecturer: Dr K.McCullagh Physiology CLASSIFICATION OF THE TYPES OF MUSCLES (Somatic Nervous System) (Autonomic Nervous System, ANS) The three types of muscles  Smooth Muscle Widely distributed throughout body: Hollow internal organs and tubes; Vascular, gastrointestinal, urinary, respiratory, and reproductive tracts – Produce peristaltic waves to propel contents of these organs Ocular: Pupil of eye (ciliary muscles) Dermal: attached to the base of hair follicles; pilo motor muscles Influence the movement of material into, out of and within the body Involuntary control; responds to autonomic innervation, spontaneous contraction, modulated by the endocrine system Hollow Internal Organs Dilation Constriction  Smooth Muscle No sarcomere, but something analogous to a sarcomere Long actin filaments attached to dense bodies (analogous to Z-discs) Some myosin filaments Amount of Sarcoplasmic Reticulum varies and is less organized No Transverse-tubules Arrangement allows contraction even when greatly stretched Smooth Muscle Smooth muscle organization Myosin filaments longer than in Sk. Muscle. Entire length covered with myosin heads. Unique arrangement allows force development even when greatly stretched e.g. filling of bladder. D.U. Silverthorn, Human Physiology Smooth muscles (SMs) can be classified by contraction pattern Phasic Smooth muscles : undergo periodic contraction and relaxation cycles e.g. Esophagus Wall of the intestine Tonic Smooth muscles : continuously contracted (always maintaining some tone) e.g. Esophageal sphincter Urinary bladder sphincter These sphincters relax to allow material to enter or leave the organ. Smooth muscle contractions Phasic SM Tonic SM D.U. Silverthorn, Human Physiology Smooth and skeletal muscle mechanical characteristics compared. Sk. Muscle Smooth Muscle Smooth and skeletal muscle mechanical characteristics compared  Excitation-Contraction Coupling in Smooth Muscle Begins with rise in intracellular calcium concentrations – Only some comes from Sarcoplasmic Reticulum (SR). – Most of the calcium comes from the extracellular fluid (ECF), crossing the plasma membrane, through differentially responsive calcium channel proteins e.g. voltage-gated calcium channels open. Calcium binds to calmodulin (no troponin in smooth muscle). To relax, the Ca2+ has to be removed either to the SR or back to the ECF.  Calcium Initiates Smooth Muscle Contraction Contraction caused by electrical signaling is electromechanical coupling Contraction caused by chemical signaling is pharmacomechanical coupling Sarcoplasmic Ca2+ release Ryanodine receptor (RyR) calcium release channel IP3-receptor channel Calcium-induced calcium release (CICR) Store-operated Ca2+ channels  Cell Membrane Calcium Entry 1. Voltage-gated Ca2+ channels 2. Ligand-gated Ca2+ channels, or receptor-operated calcium channels (ROCC) 3. Stretch-activated calcium channels Open when pressure or other force distorts cell membrane (e.g. bladder filling with urine from kidney) Myogenic contraction Some smooth muscles have unstable membrane potentials – Slow-wave potentials – Pacemaker potentials  Routes of calcium entry and exit in smooth muscle IP3 is a 2nd messenger  Clinical Implications Ca2+ channel blockers – nifedipine – Cause smooth muscle relaxation – Dilation of blood vessels – Treatment of hypertension and angina nifedipine  Myosin Phosphorylation Controls Contraction Increase in cytosolic Ca2+ initiates contraction - From SR and ECF Ca2+ binds calmodulin Initiates cascade resulting phosphorylation of myosin light chains (MLC) – Calmodulin actives myosin light chain kinase (MLCK) – MLCK phosphorylates MLC Enhances myosin ATPase activity Dephosphorylation due to myosin light chain phosphatase (MLCP) – Dephosphorylated myosin may remain attached to actin for a period of time during a latch state* (see next slide) Contraction is determined by the ratio of MLCK/MLCP activity, and not by a Ca2+-troponin-tropomyosin interaction as in striated muscle Smooth Muscle Contraction and its Control 19 Smooth Muscle Contraction and Relaxation D.U. Silverthorn, Human Physiology  *The ‘Latch State’ Dephosphorylation of myosin does not automatically result in relaxation. Under conditions we do not fully understand, dephosphorylated myosin may remain in an isometric contraction called a latch state. This latch state condition allows smooth muscle cells to maintain tension while consuming low amounts of ATP It is a significant factor in the ability of smooth muscles to sustain contractions without fatiguing  Membrane potentials vary in smooth muscle Some smooth muscles have unstable membrane potentials Slow-wave potentials Pacemaker potentials D.U. Silverthorn, Human Physiology Membrane potentials vary in smooth muscle D.U. Silverthorn, Human Physiology  Types of Smooth Muscle Single-unit* smooth muscle: multiple gap junctions that make neighboring cells behave as a unit – Most smooth muscles are single-unit. – They display pacemaker activity moderated by stretch or autonomic innervation. – Only a few cells in a single-unit receive acetylcholine stimulation. *Analogous to single unit behaving atrial or ventricular myocardium.  Types of Smooth Muscle Multi-unit* smooth muscles: require individual nerve innervation (no pacemaker activity) – Few or no gap junctions – Arrector pili muscles in skin and ciliary muscles in eyes are multi-unit *Analogous to innervation of skeletal muscle  Autonomic Innervation Neurotransmitter is released along the length of an autonomic neuron from varicosities. – A number of smooth muscle cells are stimulated at once. – Form synapses en passant Types of SMs & Autonomic Innervation Single-unit SMs are connected by gap junctions, and the cells contract as a single unit. Allows more coordinated contraction. Multiunit SMs are not electrically linked, and each cell must be stimulated independently Electrical isolation of cells allows finer motor control  Smooth muscle innervation Many smooth muscle groups contract spontaneously. This activity can be modulated by the ANS Dual innervation by ANS (sympathetic and parasympathetic) allows for up- and down- regulation of autorhythmic activity Parasympathetic - Sympathetic* - depending on tissue can ↑ or ↓ activity *Dependent of alpha versus beta adrenergic receptor expression levels  Autonomic Effects on Selected Smooth Muscles Muscarinic Receptors D.U. Silverthorn, Human Physiology Duration of muscle twitch in the three types of muscle Smooth muscles are the slowest to contract and relax Skeletal Cardiac Smooth Tension 0 1 2 3 4 5 Time (sec)  Summary of smooth muscle characteristics compared to skeletal muscle 1. Smooth muscles must operate over a range of lengths 2. Within an organ, the layers may run in several directions 3. Smooth muscles contract and relax much more slowly 4. Smooth muscle uses less energy to generate and maintain a given amount of force 5. Smooth muscle can sustain contractions for extended periods without fatiguing 6. Smooth muscles have small, spindle-shaped cells with a single nucleus  Smooth Muscle is More Variable Than Skeletal Muscle 7. The contractile fibers are not arranged in sarcomeres 8. Contraction in smooth muscle may be initiated by electrical or chemical signals or both 9. Smooth muscle is controlled by the autonomic nervous system 10. Smooth muscle lacks specialized receptor regions 11. The Ca2+ for contraction comes from the extracellular fluid as well as from the sarcoplasmic reticulum 12. The Ca2+ signal initiates a cascade that ends with phosphorylation of myosin light chain and activation of myosin ATPase  Comparison of the Three Muscle Types Blank Skeletal Smooth Cardiac Appearance under Light Striated Smooth Striated Microscope Fiber Arrangement Sarcomeres No Sarcomeres Sarcomeres Location Attached to bones; a few sphincters Forms the walls of hollow organs Heart muscle close off hollow organs and tubes; some sphincters Tissue Morphology Multinucleate; large, cylindrical Uninucleate; small spindle- Uninucleate; shorter branching fibers shaped fibers fibers Internal Structure T-tubule and sarcoplasmic reticulum No t-tubules; sarcoplasmic T-tubule and sarcoplasmic (SR) reticulum reticulum Fiber Proteins Actin, myosin; troponin and Actin, myosin; tropomyosin Actin, myosin; troponin and tropomyosin tropomyosin Continued… D.U. Silverthorn, Human Physiology  Comparison of the Three Muscle Types Blank Skeletal Smooth Cardiac Control Ca2+ and troponin Ca2+ and calmodulin Ca2+ and troponin Fibers independent of one Some fibers electrically linked Fibers electrically linked via gap another via gap junctions; others junctions independent Ca2+ from S R Ca2+ from E CF and SR Ca2+ from E CF and SR Contraction Speed Fastest Slowest Intermediate Contraction Force of Single Not graded Graded Graded Fiber Twitch Initiation of Contraction Requires ACh from motor neuron Stretch, chemical signals. Can Autorhythmic be autorhythmic Neural Control of Somatic motor neuron Autonomic neurons Autonomic neurons Contraction Hormonal Influence on None Multiple hormones Epinephrine Contraction D.U. Silverthorn, Human Physiology