Physiology of Smooth Muscle PDF

PHYSIOLOGY OF SMOOTH MUSCLE -4-  SMOOTH MUSCLE PHYSIOLOGY Gastrointestinal canal Respiratory airways “Major component of hollow organs” Urogenital tract Vasculature  SMOOTH MUSCLE Peristaltism Vasoconst...

PHYSIOLOGY OF SMOOTH MUSCLE -4-  SMOOTH MUSCLE PHYSIOLOGY Gastrointestinal canal Respiratory airways “Major component of hollow organs” Urogenital tract Vasculature  SMOOTH MUSCLE Peristaltism Vasoconstriction Many of the basic muscle properties are highly modified in smooth muscle, because of the very different functional roles it plays in the body (smooth muscle is an integral component of the body).  FUNCTIONS OF SMOOTH MUSCLE The motility of stomach intestine movements.  To excrete the bladder and urine  The activitiy of bronchus and respiratory system  Uterus contractions, mensturation, labour.  In eye, Mydriasis (dilation of the pupil), Miosis (constriction of pupil), Acommodation  Arteries-regulation of blood pressure  PROPERTIES OF SMOOTH MUSCLE While there are major differences among the organs and systems in which smooth muscle plays a major part, the structure of smooth muscle is quite consistent at the tissue level and even more similar at the cellular level. High metabolic economy of smooth muscle! Allows it to remain contracted for long periods with little energy consumption! Small size of smooth muscle cells, Allows precise control of very small structures, (such as blood vessels) Circular Organization: (Blood vessels) The simplest smooth muscle arrangement is found in the arteries and veins of the circulatory system. Shortening of the fibers results in reducing the vessel’s diameter (vasocontraction). This circular arrangement is also prominent in the airways of the lungs and also in sphincters. Undeveloped sarcoplasmic reticulum (SR) (contains SR but very primitive one) Contains thin and thick filaments, but nospecific sarcomere structure Centrally located nucleus NO T-tubule (Transverstubule)! THE PROPERTIES OF NO troponin complex! SMOOTH MUSCLE NO neuromuscular junction! Usually 1 to 5 micrometers (𝝁m) in diameter and only 20 to 500 micrometers in length. Many of the same principles of contraction apply to smooth muscle as to skeletal muscle.  The internal physical arrangement of smooth muscle fibers is different (nostriatedappearance)  Types of Smooth Muscle Smooth muscle can generally be divided into two major types, * multi-unit smooth muscle and * unitary (or single-unit) smooth muscle Unitary Smooth Muscle *Called syncytial smooth muscle or visceral smooth muscle. *A mass of hundreds to thousands of smooth muscle fibers that contract together as a single unit. *Arranged 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 can flow freely from one muscle cell to the next. This type of smooth muscle is also known as syncytial smooth muscle because of its syncytial interconnections among fibers. Unitary Smooth Muscle called visceral smooth muscle because it is Have extensive intercellular electrical found in the walls of most viscera of the body, communication including the gastrointestinal tract, bile ducts, ureters, uterus, and many blood vessels.  *Composed of discrete, separate smooth Multi-Unit Smooth Muscle muscle fibers. *Each fiber operates independently of the others *Each fiber is innervated by a single nerve ending, as occurs for skeletal muscle fibers. *The outer surfaces of these fibers, are covered by a thin layer of basement membrane–like substance, a mixture of fine collagen and glycoprotein that helps insulate the separate fibers from one another. *The cells of multi-unit smooth muscle are not linked electrically. Each individual muscle fiber must be closely associated with an axon terminal or varicosity. - ciliary muscle of the eye, - the iris muscle of the eye, - the piloerector muscles  CONTRACTILE MECHANISM IN SMOOTH MUSCLE *Contains actin and myosin filaments, *Chemical characteristics of actin and myosin filaments similar within skeletal muscle, interact with each other in much the same way that they do in skeletal muscle. *No troponin complex, so the mechanism for control of contraction is entirely different. *The contractile process is activated by calcium ions, and adenosine triphosphate (ATP) is degraded to adenosine diphosphate (ADP) to provide the energy for contraction. *Major differences between the physical organization of smooth muscle and that of skeletal muscle, as well as differences in excitation-contraction coupling, control of the contractile process by calcium ions, duration of contraction, and amount of energy required for contraction. * There is no same striated arrangement of actin and myosin filaments similar with skeletal muscle. Instead, large numbers of actin filaments attached to structure called dense bodies (dense bodies are the functional equivalents of the Z lines). *Some of dense bodies are attached to the cell membrane. *Others are dispersed inside the cell. *Some of the membrane-dense bodies of adjacent cells are bonded together by intercellular protein bridges. It is mainly through these bonds that the force of contraction is transmitted from one cell to the next. *Myosin filaments has a location between actin filaments. Myosin have a diameter more than twice that of the actin filaments. *Number of actin filaments are 5 to 10 fold bigger than myosin filaments.  Cell-to-Cell Contacts Smooth muscle cells are connected to each other 1.Gap junctions – Low-resistance pathways – Action potentials can readily propagate 2.Adherens junctions (dense bodies) – Provide mechanical linkage – Dense granular material – Thin filaments extend into the adherens junction  COMPARISON OF SMOOTH MUSCLE CONTRACTION AND SKELETAL MUSCLE CONTRACTION 1. Slow Cycling of the Myosin Cross-Bridges The rapidity of cycling of the myosin cross-bridges in smooth muscle—that is, their attachment to actin, then release from the actin, and reattachment for the next cycle—is much slower than in skeletal muscle. (remaining the cross-bridges attached to the actin filaments, is a major factor which determines the force of contraction, so, it is greatly increased in smooth muscle). 2. Low Energy Requirement to Sustain Smooth Muscle Contraction Only 1/10 to 1/300 as much energy is required to sustain the same tension of contraction in smooth muscle as in skeletal muscle. This is result from the slow attachment and detachment cycling of the cross-bridges and because only one molecule of ATP is required for each cycle, regardless of its duration. 3. Slowness of Onset of Contraction and Relaxation of the Total Smooth Muscle Tissue. The slow onset of contraction prolonged contraction, is caused by the slowness of attachment and detachment of the cross-bridges with the actin filaments. In addition, the initiation of contraction in response to calcium ions is much slower than in skeletal muscle, is about contraction mechanism*** 4. Maximum Force of Contraction Is Often Greater in Smooth Muscle Than in Skeletal Muscle. Despite the relatively few myosin filaments in smooth muscle, and despite the slow cycling time of the cross-bridges, the maximum force of contraction of smooth muscle is often greater than that of skeletal. This greater force of smooth muscle contraction results from the prolonged period of attachment of the myosin cross-bridges to the actin filaments. 1. Slow Cycling of the Myosin Cross-Bridges. 2. Low Energy Requirement for contraction 3. Slowness of Onset of Contraction and Relaxation 4. Greater Maximum Force Because most smooth muscles must function for long periods without rest, their power output is relatively low, but contractions can continue without using large amounts of energy. Some smooth muscle can also maintain contractions even as Ca++ is removed and myosin kinase is inactivated/dephosphorylated. This can happen as a subset of cross-bridges between myosin heads and actin, called latch- bridges, keep the thick and thin filaments linked together for a prolonged period, and without the need for ATP. This allows for the maintaining of muscle “tone” in smooth muscle that lines arterioles and other visceral organs with very little energy expenditure.  NO T-tubule (Transvers tubule)!  NO troponin complex! NO neuromuscular junction! Calmodulin instead of Troponin complex Caveolae instead of T-tubule Varicosites instead neuromuscular junction *Keeps calcium close to the membrane. Neuromuscular junctions of the highly structured type found on skeletal muscle fibers do not occur in smooth muscle. Instead, the autonomic nerve fibers that innervate smooth muscle generally branch diffusely on top of a sheet of muscle fibers.  VARICOSITES Varicosites instead of What are varicosities? neuromuscular junction Expanded axon parts or, numerous bulbous swellings in smooth muscle; release neurotransmitter into a wide synaptic cleft in the general area of the smooth muscle cells. Such junctions are called diffuse junctions. Is smooth muscle Excitated, Inhibited, or Both? HOW? (Please remember, skeletal muscle is only Excitated!) Excitatory, Inhibitory issue is depends on the NT inside the varicosites!  Excitatory and Inhibitory Transmitter Substances Secreted at the Smooth Muscle Neuromuscular Junction (varicosites) The most important transmitter substances secreted by the autonomic nerves innervating smooth muscle are acetylcholine and norepinephrine, but they are never secreted by the same nerve fibers. Acetylcholine is an excitatory transmitter substance for smooth muscle fibers in some organs but an inhibitory transmitter for smooth muscle in other organs. When acetylcholine excites a muscle fiber, norepinephrine ordinarily inhibits it. Conversely, when acetylcholine inhibits a fiber, norepinephrine usually excites it. But why are these responses different? The answer is that both acetylcholine and norepinephrine excite or inhibit smooth muscle by first binding with a receptor protein on the surface of the muscle cell membrane. Some of the receptor proteins are excitatory receptors, whereas others are inhibitory receptors. Thus, the type of receptor determines whether the smooth muscle is inhibited or excited and also determines which of the two transmitters, acetylcholine or norepinephrine, is effective in causing the excitation or inhibition.  “The Regulation and Control of Smooth Muscle Involve Many Factors” Smooth muscle is subject to a much more complex system of controls than skeletal muscle. In addition to contraction in response to nerve stimulation, smooth muscle responds to hormonal and pharmacological stimuli, the presence or lack of metabolites, cold, pressure, and stretch, or touch, and it may be spontaneously active as well. Innervation of Smooth Muscle; Most smooth muscles have a nerve supply, usually from both divisions of the autonomic nervous system. Autonomic nerve axons run throughout the tissue; along the length of the axons are many swellings or varicosities, which are the sites of release of transmitter substances in response to nerve action potentials. Released molecules of excitatory or inhibitory transmitter diffuse from the nerve to the nearby smooth muscle cells, where they take effect. Neuromuscular transmission  INNERVATION A smooth muscle cell may receive input from more than one neuron  Source of Calcium Ions In smooth muscle there is a few slightly developed sarcoplasmic tubules. The calcium storage function of the SR is supplemented by caveolae, small vesicles that cluster close to the cell membrane. The membranes of caveolae contain gated Ca2+ channels that open in response to either – a change in membrane potential or – the binding of a ligand When the channels open, Ca2+ concentrated inside the caveolae enters the cell. In smooth muscle, Ca2+ enters from the extracellular fluid in addition to being released from the SR. Major Routes Of Calcium Entry And Exit From The Cytoplasm Of Smooth Muscle Activation of Smooth Muscle Contraction; Chemical factors control the function of smooth muscle cells Some factors act by opening or closing cell Others result in production of a second membrane ion channels. messenger that diffuses to the interior of the cell, where it causes further changes. The final result of both mechanisms is usually a change in the intracellular concentration of Ca, which, in turn, controls the contractile process itself.  Membrane Potentials and Action Potentials in Smooth Muscle Membrane Potentials in Smooth Muscle The quantitative voltage of the membrane potential of smooth muscle depends on the momentary condition of the muscle. In the normal resting state, the intracellular potential is usually about −50 to −60 millivolts. (which is about 30 millivolts less negative than in skeletal muscle.) Action Potentials in Unitary Smooth Muscle Action potentials occur in unitary smooth muscle (such as visceral muscle) in the same way that they occur in skeletal muscle. The action potentials of visceral smooth muscle occur in one of two forms: (1) spike potentials or (2) action potentials with plateau. 1. Typical spike action potentials Typical spike action potentials, such as those seen in skeletal muscle, occur in most types of unitary smooth muscle. The duration of this type of action potential is 10 to 50 milliseconds. Such action potentials can be elicited in many ways, for example, * by electrical stimulation, * by the action of hormones on the smooth muscle, * by the action of transmitter substances from nerve fibers, *by stretch, or as a result of spontaneous generation in the muscle fiber itself, The resting potential of most smooth muscles is approximately -50 mV. This is less negative than the resting potential of nerve and other muscle types, it is determined primarily by the transmembrane potassium ion gradient. The smaller potential (-50 mV) is due primarily to a greater resting permeability to sodium ions. 2. Action Potentials with Plateau The onset of this action potential is similar to that of the typical spike potential. However, instead of rapid repolarization of the muscle fiber membrane, the repolarization is delayed for several hundred to as much as 1000 milliseconds (1 second). The importance of the plateau is that it can account for the prolonged contraction that occurs in some types of smooth muscle, such as the ureter, the uterus under some conditions, and certain types of vascular smooth muscle. (Also, this is the type of action potential seen in cardiac muscle fibers that have a prolonged period of contraction) Phase 0: Resting membrane potential; outward potassium current. Phase 1,2 the rising phase (upstroke depolarization); activates voltage-gated calcium channels, voltage-gated sodium channels and voltage-gated potassium channels. Phase 3, the plateau phase; balances inward calcium current and outward potassium current. Phase 4, the falling phase (repolarization), inactivates voltage-gated calcium channels and activates calcium-gated potassium channels. Slow Wave Potentials in Unitary Smooth Muscle Can Lead to Spontaneous Generation of Action Potentials. Some smooth muscle is self-excitatory. That is, action potentials arise within the smooth muscle cells themselves without an extrinsic stimulus. This is often associated with a basic slow wave rhythm of the membrane potential. *The slow wave itself is not the action potential. *The importance of the slow waves is that, when they are strong enough, they can initiate action potentials. The slow waves themselves cannot cause muscle contraction. A typical slow wave in a visceral smooth muscle of the gut Electrical slow-wave frequencies; Slow waves with similar waveforms occur at different frequencies in the stomach, small intestine, and colon. In many smooth muscles, the resting potential varies periodically with time, producing a rhythmic potential change called a slow wave.  The mechanism of excitation-contraction coupling in smooth muscle differs from that of skeletal muscle. Recall that in skeletal muscle binding of actin and myosin is permitted when Ca2+ binds troponin C.  In smooth muscle, however, there is no troponin. Rather, the interaction of actin and myosin is controlled by the binding of Ca2+ to another protein, calmodulin. In turn, Ca2+-calmodulin regulates myosin-light-chain kinase, which regulates cross-bridge cycling.  CONTRACTION OF SMOOTH MUSCLE RELAXATION OF SMOOTH MUSCLE  Effect of Local Tissue Factors and Hormones to Cause Smooth Muscle Contraction Without Action Potentials Two types of non-nervous and nonaction potential stimulating factors often involved are (1) local tissue chemical factors and (2) various hormones. 1.Lack of oxygen in the local tissues Many circulating hormones in the causes smooth muscle relaxation and, blood and neurotransmitter affect therefore, vasodilatation. smooth muscle contraction 1.Norepinephrine, 2.Excess carbon dioxide 2.Epinephrine, 3.Acetylcholine, 3.Increased hydrogen ion concentration 4.Angiotensin, 5.Endothelin, Adenosine, lactic acid, increased 6.Vasopressin, potassium ions, diminished calcium ion 7.Oxytocin, concentration, and increased body 8.Serotonin, temperature can all cause local 9.Histamine. vasodilatation.  Comparison of Smooth Muscle Contraction and Skeletal Muscle Contraction Feature Smooth Muscle Skeletal Muscle Cell Structure Small, spindle-shaped cells, no striations. Large, cylindrical, multinucleated cells, striated. Involuntary, controlled by the autonomic nervous system, hormones, and Control Voluntary, controlled by the somatic nervous system. local factors. Slow and sustained contractions. Can hold contractions for long periods Fast contractions designed for rapid, short bursts of activity (e.g., Speed of Contraction (e.g., vascular tone). movement of limbs). Calcium comes from both the extracellular fluidand the sarcoplasmic Calcium Source Calcium is primarily released from the sarcoplasmic reticulum (SR). reticulum (SR). Calmodulin binds calcium and activates myosin light chain kinase (MLCK), Troponin binds calcium, causing a conformational change in tropomyosin Calcium-Binding Protein initiating contraction. that allows actin-myosin interaction. Contraction can be triggered by mechanical stretch, electrical signals, or Contraction is triggered by an action potentialfrom motor neurons leading Initiation of Contraction chemical signals (e.g., hormones, neurotransmitters). to depolarization of the muscle fiber membrane. Highly energy-efficient. Can maintain force with low ATP consumption, Less energy-efficient compared to smooth muscle, requires continuous Energy Efficiency especially in the "latch state." ATP during contraction. Can maintain contraction for long periods without fatigue (e.g., bladder, Contraction Duration Contracts quickly but fatigues easily with prolonged activity. blood vessels). Regulated by phosphorylation of myosin light chains through MLCK and Regulated by the interaction between actin and myosin, initiated by the Regulation of Contraction MLCP. removal of tropomyosin inhibition. Produces less force than skeletal muscle but sustains force for longer Force Production Produces high force in short bursts for rapid and strong movements. periods. More variable; slow wave potentials or depolarization can initiate A stable resting membrane potential, action potentials are required for Resting Membrane Potential contraction without a defined action potential. contraction. Typically tonic (maintaining tension over time) or phasic (rhythmic Phasic, meaning it contracts quickly and then relaxes (e.g., twitch Types of Contraction contractions). contraction). Cells are connected by gap junctions in single-unit smooth muscle, Each muscle fiber is controlled individually by its own motor neuron (no Cell Communication allowing synchronized contractions. gap junctions). Fatigues faster during extended periods of activity, though training can Fatigue Resistance Extremely fatigue-resistant, can maintain contractions for long periods. improve endurance. Smooth muscle cells can regenerate to some extent through hyperplasia Limited regeneration; skeletal muscle heals primarily through hypertrophy Regeneration Capacity and hypertrophy. (growth of existing cells). Found attached to bones, controlling voluntary movements (biceps, Examples Found in walls of hollow organs (blood vessels, intestines, uterus, bladder). quadriceps).