Copyright © 2010 Pearson Education, Inc. Smooth muscle physiology  Organizational structure & function  Excitation contraction coupling

Copyright © 2010 Pearson Education, Inc. Smooth Muscle anatomy Smooth muscle is considered to be much more primitive than either cardiac or skeletal muscle. Muscle striations are not visible in smooth muscle, so the sarcomere relationship of myosin to actin does not exists in smooth muscle. However, per cross sectional area smooth muscle is as strong as skeletal muscle and smooth muscle is highly resistant to fatigue.

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Anatomy I. Smooth Muscle 1. Fibers are smaller than skeletal muscle 2. Involuntary (Usually) 3. No apparent myofibrils under the light microscope - No cross striations 4. Fibers are thickest in the middle and have tapered ends 5. Centrally located single oval nucleus

Copyright © 2010 Pearson Education, Inc. Smooth Muscle anatomy

Copyright © 2010 Pearson Education, Inc. Smooth Muscle anatomy 6. Sarcoplasm contains thick and thin filaments a. Not in an orderly pattern b. there are 10 – 20 times more thin filaments than thick filaments 7. Dense bodies a. Have thin filaments attached to them b. Function is similar to Z disks c. Dispersed throughout the sarcoplasm or attached to the sarcolemma d. Thin filaments stretch from one dense body to another

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Anatomy

Copyright © 2010 Pearson Education, Inc. B. Generation of Contraction 1. Sliding filament mechanism involving thick and thin filaments generates tension that is transmitted to the thin filaments 2. Does not contain Troponin complex 3. Actin and myosin pull on the dense bodies attached to the sarcolemma 4. Shortening of the smooth muscle fiber is lengthwise, the middle of the fiber thickens Smooth Muscle anatomy

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Anatomy

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Anatomy 5. Shortening causes bubble like expansion of the sarcolemma 6. Shortening is corkscrew like - the fiber twists in a helix as it shortens and rotates in the opposite direction as it lengthens

Copyright © 2010 Pearson Education, Inc. Types of smooth muscles Single Unit - Large aggregates of smooth muscle cells which act as a single unit. Multi Unit - Single smooth muscle cells usually with a single nerve connection

Copyright © 2010 Pearson Education, Inc. Types of smooth muscles

Copyright © 2010 Pearson Education, Inc. Types of smooth muscles A. Multi-unit smooth muscle Composed of discrete,separate smooth muscle fibers Each fiber operate/contract independently of others Often innerveted by a single nerve ending as occurs for skeletal muscles Their control is exerted mainly by the nerve signals Outer surface are Covered by a thin layer of basement membrane of fine collagen and glycoprotein fibrillae that help to insulate the separate fibers from one another Examples: the ciliary & iris muscles of the eye; the piloerector muscles that cause erection of the hairs when stimulated by the sympathetic nervous system

Copyright © 2010 Pearson Education, Inc. Types of smooth muscles B. Single Unit - Unitary Smooth Muscle - (Syncytial smooth muscle or visceral smooth muscle) Is a mass of hundreds to thousands of smooth muscle fibers that contract as a single unit The fibers are aranged in sheets or bundles and their cell membranes are adherent to one another at multiple points so that force generated in one muscle fiber can be transmitted to the next The cell membranes are joined by many gap junctions through which ions flow freely from one muscle cell to the next so that action potentials or simple ion flow without ion potentials can travel from one fiber to the next and cause muscle fibers to contract together

Copyright © 2010 Pearson Education, Inc. Types of Smooth Muscle Response to different types of stimuli Nerves, hormones, mechanical stretch, endothelial mediators (EDNO) Location Form part of the walls of both large and small arteries and veins Hollow viscera - Stomach, intestines, uterus, urinary bladder,bile ducts etc Muscle forms large networks and an action potential causes contraction of the entire organ

Copyright © 2010 Pearson Education, Inc. Function Control the size of organs cause the release of substances Control the rate of flow (blood, contents of GI tract, urine) - etc.

Copyright © 2010 Pearson Education, Inc. Multi vs. Single-Unit Muscle

Copyright © 2010 Pearson Education, Inc. comparison of smooth muscle contraction & skeletal muscle contraction Most skeletal muscles contract and relax rapidly as compared to Most smooth muscle contraction which is prolonged tonic contraction sometimes lasting hours or even days This is caused by their differences in chemical and physical properties 1.Slow cycling of the myosin cross bridges 2.Low energy requirement to sustain smooth muscle contraction 3.Slowness of onset of contraction and relaxation of the total smooth muscle tissue 4.Maximum force of contraction is often greater in smooth muscle than in skeletal muscle

Copyright © 2010 Pearson Education, Inc. comparison of smooth muscle contraction & skeletal muscle contraction 5.Latch Mechanism - prolonged holding in smooth muscle After contraction is initiated, less stimulus and energy are needed to maintain the contraction (Energy conservation) Can maintain prolonged tonic contractions for hours with little energy and little excitatory signal from nerves or hormones Mechanism: lower activation of enzymes, myosin head remains attached to actin for long periods of time but large numbers are attached and the force is great

Copyright © 2010 Pearson Education, Inc. comparison of smooth muscle contraction & skeletal muscle contraction 6.Stress - Relaxation of Smooth Muscle Important characteristic of visceral smooth muscle Stress - Relaxation response - ability to return nearly to its original force of contraction seconds or minutes after it has been elongated or shortened When smooth muscle is initially stretched - it will contract and increase tension (Myogenic response) Smooth muscle fibers can stretch and still maintain their contractile function

Copyright © 2010 Pearson Education, Inc. comparison of smooth muscle contraction & skeletal muscle contraction Smooth muscle can undergo great changes in length and still retain the ability to contract effectively This response allows vessels and hollow organs to change size but maintain the pressure within the structure at a constant level (Probably related to the “latch mechanism”)

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Contractile Mechanism Contractile Process in Smooth Muscle 1. Chemical basis for smooth muscle contraction a. Contains actin and myosin filaments similar in structure and interaction to skeletal muscle b. No troponin complex - mechanism for contraction is different c. Calcium influx activates the contractile process d. ATP provides energy for contraction

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Contractile Mechanism Regulation of Contraction by Calcium Ions ICF calcium is the initiating event for smooth muscle contraction An increase in calcium influx can be caused by: nerve stimulation Hormones chemical changes in the environment (Ligands) mechanical stretch of the fiber

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Contractile Mechanism Role of calmodulin in excitation- contraction-coupling in smooth muscle a. Smooth muscle has no Troponin but it does have a regulatory protein called calmodulin b. Calmodulin is similar in structure to Troponin and like Troponin combines with 4 calcium ions causing activation c. Activated calmodulin-Ca++ complex activates myosin light chain kinase

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Contractile Mechanism d. The activated myosin light chain kinase phosphorylates the myosin light chains (regulatory proteins on the myosin heads) using an ATP unit e. The myosin heads now engage actin and cross bridge cycling proceeds using the same process as in skeletal muscle f. Cessation of contraction 1. As [Ca++] drops below a critical level 2. Myosin phosphatase removes the phosphate from the myosin light chains and contraction stops

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Cell

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Contraction: Mechanism

Copyright © 2010 Pearson Education, Inc. Smooth Muscle Relaxation: Mechanism

Copyright © 2010 Pearson Education, Inc. SMOOTH MUSCLE STIMULATION Smooth muscle responds to stimulation from a number of different physiological systems. 1. Nerves 2. Hormones 3. Mechanical manipulation 4. Self stimulation (Automaticity)

Copyright © 2010 Pearson Education, Inc. SMOOTH MUSCLE Neural-Muscular Junction

Copyright © 2010 Pearson Education, Inc. SMOOTH MUSCLE STIMULATION Excitatory and inhibitory transmitter substances at NMJ a. Ach & norepinephrine are never secreted by the same nerve fiber b. Ach can be excitatory or inhibitory - determined by the type of receptor expressed by the target cell c. Ach and NE usually cause the opposite reaction at a target cell (If Ach is stimulatory then NE will most likely be inhibitory)

Copyright © 2010 Pearson Education, Inc. SMOOTH MUSCLE STIMULATION Unitary Membrane Potential and AP in smooth muscle (Slow waves and Spike Potentials) Unitary smooth muscle a. Slow waves - In smooth muscle the resting membrane potential is variable - usually about -50 to -60 mV b. Variable resting membrane potential is called the basic electrical rhythm or BER or sometimes slow waves

Copyright © 2010 Pearson Education, Inc. SMOOTH MUSCLE STIMULATION Unitary

Copyright © 2010 Pearson Education, Inc. SMOOTH MUSCLE STIMULATION Unitary Slow waves and spontaneous generation of action potentials 1. Slow waves are not action potentials - they are local unstable resting membrane potential and they determine the rhythmicity of smooth muscle contractions 2. Slow waves can initiate true action potentials called spike potentials (Ca++ voltage gated) 3. Spike potentials are generated whenever BER exceeds threshold about -35 mV

Copyright © 2010 Pearson Education, Inc. SMOOTH MUSCLE STIMULATION Unitary Spike Potentials a) Spike potentials cause rhythmic contractions of smooth muscle b) Increase the number of spike potentials and increase the force of smooth muscle contraction c) Regulation - mechanical stretch, hormones, and Ach cause membrane to become less negative (Hypopolarize the cells)

Copyright © 2010 Pearson Education, Inc. SMOOTH MUSCLE STIMULATION Unitary

Copyright © 2010 Pearson Education, Inc. Depolarization of Multiunit Smooth Muscle w/o AP Smooth muscle contraction in response to local tissue factors 1) Arterioles, metarterioles & precapillary sphincters have little or no nerve supply 2) Highly contractile smooth muscle responds rapidly to local factors Lack or a decrease in O2 levels - Increase in CO2 - Increase in hydrogen ions - Decrease in ECF Ca++ - Adenosine or increased lactic acid – Cause Vasodilation

Copyright © 2010 Pearson Education, Inc. Depolarization of Multiunit Smooth Muscle w/o AP Effect of hormones on smooth muscle contraction 1) Most hormones affect smooth muscle through second messengers 2) Important hormones - Norepinephrine, epinephrine, Ach, angiotensin II, oxytocin, vasopressin, serotonin and histamine 3) Action of hormones is controlled by the type of receptors expressed by the target cell - hormone (Ligand) gated excitatory and inhibitory receptors (Ca++ or K+ channels)

Copyright © 2010 Pearson Education, Inc. Comparisons Among Skeletal, Smooth, and Cardiac Muscle