Muscle Physiology PDF

MUSCLE PHYSIOLOGY 5. Smooth muscle Andre Azevedo, DVM, MSc Visiting Professor of Veterinary Physiology [email protected]  Learning objectives for this lecture Describe the 2 types of smooth muscle in i t...

MUSCLE PHYSIOLOGY 5. Smooth muscle Andre Azevedo, DVM, MSc Visiting Professor of Veterinary Physiology [email protected]  Learning objectives for this lecture Describe the 2 types of smooth muscle in i the particularities THEY atintently Describe unit finemotor innervated of the smooth muscle List the 4 factors that can initiate contraction in the smooth muscle Describe the 5 steps of smooth muscle contraction Describe how the Ca pump and Myosine Phosphatase act to stop smooth muscle contraction  Smooth muscle The internal physical arrangement of smooth muscle fibers is different from skeletal muscle Smooth muscle of each organ is distinctive Physical dimensions Organization into bundles or sheets Response to different stimuli Characteristics of innervation Function  Smooth muscle The microscopic structure of smooth muscle fibers: Small cells Spindle-shaped Non-striated One central nucleus Lack of the coarse connective tissue covering skeletal muscle Arranged into sheets  peripateh Types of smooth muscle Multi-unit smooth muscle ing ife'd Discrete, separate smooth muscle fibers Each muscle fiber contracts independently Single-unit (visceral) smooth muscle Independently innervated Also called visceral, syncytial or unitary smooth muscle Locations Fibers are arranged in sheets or bundles Ciliary muscles of the eyes Cell membranes are adherent to one another Iris muscle of the eyes The force generated in one muscle fiber can be transmitted to the next Base of hair follicles Contract together as a single unit Smaller airways of lungs Cell membranes are joined by many gap junctions Walls of large blood vessels Ions can flow freely from one muscle cell to the next dens in'sthe Fibers contract together Locations Gastrointestinal tract, bile ducts, ureters, uterus, and many blood vessels  Gap junctions Allow the passage of small water-soluble molecules from cell to cell Without having to pass through the plasma membrane I.e.: ions, glucose The gap is narrow (2 – 4 nm) Very important in tissues containing electrically excitable cells Action potentials can spread rapidly from cell to cell I.e.: cardiac contraction, peristaltic movements of intestines Located in connective tissue, epithelial tissue, cardiac muscle, neurons  Smooth muscle Smooth muscle does not have the same striated arrangement of action and myosin filaments Large numbers of actin filaments attached to DENSE BODIES (Z-disk similar) Some bodies are attached to the cell membrane Some of them are bond together by intercellular protein bridges Some bodies are dispersed inside the cell NO troponin-tropomyosin complex Myosin filaments are intercalated among the actin filaments Smooth muscle  Smooth muscle Myosin filaments have side-polar cross-bridges They are arranged so that the bridges on one side bend in one direction, and those on the other side bend in the opposite direction This configuration allows the myosin to pull an actin filament simultaneously in opposite directions Smooth muscle can contract as much as 80% of their length – skeletal muscle only 30%  Smooth muscle Sarcoplasmic reticulum is slightly developed It is not the major source of Ca for smooth muscle contraction – ECF is! Not present in all smooth muscle fibers Lies near the cell membrane in some larger smooth muscle cells Small invaginations of the cell membrane, called CAVEOLAE, abut the surface of SR Rudimentary T-Tubule Is believed to excite calcium release from the abutting SR The more extensive the SR in the smooth muscle fiber, the more rapidly it contracts  Neural and hormonal control Smooth muscle can be stimulated to contract in different ways Contains many types of receptors proteins that can initiate or inhibit the contractile process The contraction can be initiated by factors like: 1. NERVOUS STIMULATION 2. HORMONAL STIMULATION 3. LOCAL TISSUE CHEMICAL FACTORS 4. SELF EXCITATION  Nervous stimulation Smooth muscle is innervated by autonomic nerve fibers The autonomic nervous system (ANS) is a division of the peripheral nervous system that influences the function of internal organs (involuntary) ANS has 2 branches – the sympathetic and the parasympathetic nervous system SNS – “fight or flight” system PNS – “rest and digest” system In many cases, they have opposite actions SNS somaticnervoussystem  Nervous stimulation In most instances, fibers do not make direct contact with the smooth muscle fiber cell membrane Form diffuse junctions that secrete their neurotransmitter into the matrix coating of the smooth muscle Neurotransmitter diffuses to the cells  Nervous stimulation Fine terminal axons have multiple VARICOSITIES Distributed along their axes Contain vesicles that store neurotransmitters Acetylcholine - PNS Norepinephrine - SNS Opposite effects Other substances, as well  Nervous stimulation MULTI-UNIT SMOOTH MUSCLE Usually, the neurotransmitter (ACh or NE) causes depolarization of the muscle membrane and contraction without generating an action potential – JUNCTIONAL POTENTIAL FIBERS ARE TOO SMALL– stimuli spreads over the entire fiber SINGLE-UNIT (VISCERAL) SMOOTH MUSCLE Action potentials occur similar to those presented on Skeletal Muscle  Action potential in visceral smooth muscle The action potentials of visceral smooth muscle occur in one of 2 forms: 1. SPIKE POTENTIALS Similar to those seen in skeletal muscle – occur in most types of visceral smooth muscle Can be elicited by electrical stimulation, hormones, stretch, or spontaneously Some smooth muscle cells are SELF EXCITATORY – AP arise without an extrinsic stimulus Associated with a basic slow wave rhythm of the membrane potential Whenever they got strong enough, they initiate an AP I.e.: rhythmical contraction of the intestinal wall The cause of the slow wave rhythm is unknown Waxing and waning pumping of positive ions (Ca, Na)?  Action potential in visceral smooth muscle The action potentials of visceral smooth muscle occur in one of 2 forms: 2. ACTION POTENTIALS WITH PLATEAU The onset is similar to that of the typical spike potential repolarization isslow Instead of rapid repolarization, the muscle fiber undergoes a delayed repolarization phase (prolonged depolarization). The importance of the plateau is that it can account for the prolonged contraction that occurs in some types of smooth muscle Ex: Ureter, uterus, vascular smooth muscle This is also the type of action potential seen in cardiac muscle fibers The smooth muscle membrane has more voltage-gated calcium channels and few voltage-gated sodium channels  Action potential in visceral smooth muscle CALCIUM IONS PERFORM TWO IMPORTANT TASKS AT ONCE Calcium channels are important in generating the APs and causing contraction Sodium has little participation in the generation of APs in most smooth muscle Flow of calcium ions to the interior of the fiber is mainly responsible for the AP Ca channels open many times more slowly than sodium channels and remain open much longer These characteristics account for the prolonged plateau AP of some smooth muscle fibers Calcium ions also act directly on the smooth muscle to cause contraction  Local tissue chemical factors In small vessels, there is little or no nerve supply Smooth muscle in these places is highly contractile Responds to changes in local chemicals conditions in the surrounding interstitial fluid and to stretch caused by changes in blood flow In resting state, many of these small vessels remain contracted When extra blood flow is needed, they relax Some of the specific control factors are: of Lack of oxygen in local tissues/excess CO2 examples Increased hydrogen ions metabolic high Increase Lactic acid Increase body temperature... demand  Hormonal stimulation Many circulating hormones in the blood affect smooth muscle contraction The target tissue must have specific receptors for the hormone Hormone-gated receptor Can be excitatory or inhibitory samecellcanhave receptors 2 Examples of hormones that affect smooth muscle: Norepinephrine, epinephrine, angiotensin II, endothelin, vasopressin, oxytocin, serotonin, and histamine  Mechanisms of chemical and hormonal excitation of smooth muscle They can stimulate contraction by the opening of Na and Ca ion channels Depolarize the membrane in the same way nerve stimulation does Inhibition occurs when they close the Na and Ca channels Some hormones can activate membrane receptors that use 2nd messengers Calcium cAMP cGMP Intracellular calcium is a major second messenger system Many extracellular signals trigger an increase in cytosolic Ca2+ Ca2+ concentration in the cytoplasm is very low Ca2+ concentration in ECF and lumen of the ER (also SR in muscle) is high There is a large gradient tending to drive Ca2+ into the cytosol across those membranes Increases can be easily detected and activates Ca2+-responsive proteins in the cell  Contraction of smooth muscle Regardless of the initial stimulus, the smooth muscle contraction will start after an increase in intracellular calcium ions Can be caused by any of the mechanisms already cited Ex.: Nerve stimulation, hormonal stimulation, local chemical tissue factors, or self-excitation Since there is no troponin complex, the contraction is activated by an entirely different mechanism Calcium ions combine with CALMODULIN to activate myosin cross-bridges CALMODULIN is a regulatory protein Functions as a multipurpose intracellular Ca2+ receptor When activated by Ca binding, it undergoes a conformational change Then will bind to and activate other proteins  Contraction of smooth muscle The activation of myosin and contraction occurs in 5 steps: 1. Calcium concentration in the cytosol increases Influx from ECF (most important) Release from the SR (only slightly developed) 2. Calcium ions bind reversibly with calmodulin 3. The Ca-calmodulin complex joins with and activates MYOSIN LIGHT CHAIN KINASE (MLCK) A phosphorylating enzyme 4. MLCK phosphorylates one of the light chains of each myosin head (REGULATORY CHAIN) 5. Contraction  Contraction of smooth muscle The activation of myosin and contraction occurs in 5 steps: 4. MLCK phosphorylates one of the light chains of each myosin head (REGULATORY CHAIN) This chain is responsible for the attachment-detachment cycling of the myosin When not phosphorylated, it does not occur When phosphorylated, has the capacity to bind repetitively with the actin filament and proceeding to the entire cycling process of intermittent pulls REGULATORY LIGHT CHAIN  Contraction of smooth muscle The activation of myosin and contraction occurs in 5 steps: 5. Contraction Depends on extracellular calcium concentration Activated (phosphorylated) myosin hydrolases ATP (ADP + Pi) Myosin binds to actin (crossbridge attachment) Phosphate released + power stroke + ADP released Rigor state (myosin and actin bound) ATP bounds to myosin, releasing actin The cycle starts again... 1018 safe Contraction of smooth muscle  Relaxation of smooth muscle A calcium pump is required to promote smooth muscle relaxation Ca pump move Calcium ions back to the ECF or SR (if present) Requires ATP Slow acting Contraction last longer than in skeletal muscle NXC After Ca channels close and Ca pump move the Ca ions out of the cell Calcium concentration falls Activate another enzyme – MYOSIN PHOSPHATASE Located in the cytosol of smooth muscle fibers Splits the phosphate from the regulatory light chain Cycle stops, and contraction ends  Particularities of smooth muscle contraction be at s MY difference Slow cycling of the myosin cross-bridges Attachment, release, and reattachment are much slower than skeletal muscle 10 Increase the force of contraction Low energy requirements to sustain contraction Important for organs that maintain tonic muscle contraction almost indefinitely I.e: Intestines, Bladder, Gallbladder