Smooth Muscle Physiology PDF

EXCITATION AND CONTRACTION OF SMOOTH MUSCLE Dr. Arzu Temizyürek https://directorsblog.nih.gov/2013/01/16/the-beauty-of-smooth-muscle/ Classification of smooth muscle according to their activity • Tonic smooth muscles: To provide the tonus continuosly active. - smooth muscle of the vessel, - respi...

EXCITATION AND CONTRACTION OF SMOOTH MUSCLE Dr. Arzu Temizyürek https://directorsblog.nih.gov/2013/01/16/the-beauty-of-smooth-muscle/ Classification of smooth muscle according to their activity • Tonic smooth muscles: To provide the tonus continuosly active. - smooth muscle of the vessel, - respiratory system, - certain sphincters (gastrointestinal system) • Phasic smooth muscles: Contracts rhytmically and intermittently - In walls of certain gastrointestinal - uro-genital organs (uterus etc…) Smooth vs. Striated Muscle • Involuntary • In contrast, skeletal muscle fibers are as much as 30 times greater in diameter and hundreds of times as long • Same attractive forces between myosin and actin filaments cause contraction but the internal physical arrangement of smooth muscle fibers is different General Properties of Smooth Muscle Cell has 3 types of filaments 1. Thick filaments: myosin - longer than those in skeletal muscle 2. Thin filaments : - actin, - tropomyosin, - caldesmon (CaD is the actin and tropomyosin binding protein) - calponin (CaP is the actin binding protein that inhibits actomyosin ATPase activity in vitro ) CaD and CaP inhibit the ATP hydrolyze of myosin which is activated by actin 3. Intermediate filaments – Filaments of intermediate size - attach dense bodies to each other. - serve as cellular skeleton - contain proteins names as desmin, flamin, crystalin and vimentin - not directly participate in contraction • Form part of cytoskeletal framework that supports cell shape TYPES OF SMOOTH MUSCLE Generally smooth muscles can be divided into two major types: 1.multi-unit smooth muscle 2. unitary (or single-unit) smooth muscle (Single Unit) Innervation of smooth muscle by autonomic nerve fibers that branch diffusely and secrete neurotransmitter from multiple varicosities. Unitary (visceral) smooth muscle cells are connected by gap junctions so that depolarization can rapidly spread from one cell to another, permitting the muscle cells to contract as a single unit. In multiunit smooth muscle, each cell is stimulated independently by a neurotransmitter released from closely associated autonomic nerve varicosities Single Unit (Visceral) Smooth Muscle • A group of smooth muscle fibers that contract together as a single unit. • Are electrically coupled to one another via gap junctions • Often exhibit spontaneous action potentials • Are arranged in opposing sheets and exhibit stress-relaxation response - Found primarily in the walls of viscera e.g. - the musculature of the intestine, ─ the uterus, and ─ the ureters, ─ bile, ─ duct, ─ bladder ─ small arteries. Figure 12.23a (1 of 2) Single-unit smooth muscle cells are connected by gap junctions, and the cells contract as a single unit. Autonomic neuron varicosity Gap junctions Neurotransmitter Receptor Smooth muscle cell Multi-Unit Smooth Muscle ➢ Each fiber can contract independently of the others, and their control is exerted mainly by nerve signals. ➢In contrast, a major share of control of unitary smooth muscle is exerted by non-nervous stimuli. ➢ Some examples of multi-unit smooth muscle are the ciliary muscle of the eye, the iris muscle of the eye the piloerector muscles Figure 12.23b (2 of 2) Multi-unit smooth muscle cells are not electrically linked, and each cell must be stimulated independently. Eye Varicosity Neuron General Properties of Smooth Muscle • Innervated by autonomic nervous system (ANS- parasympathetic and sympathetic). ANS does not initiates smooth muscle activity but controls (accelerates or decelerates) • Many visceral organs’s smooth muscle has impulse generating pacemaker cells. • As in the eye some of the smooth muscle cells can not generate impulses by themselves. Unitary Smooth Muscle Unitary smooth muscle is also called syncytial smooth muscle or visceral smooth muscle. ➢ The fibers usually are arranged in sheets or bundles ➢ their cell membranes are adherent to one another at multiple points ➢ The cell membranes are joined by many gap junctions through which ions can flow freely from one muscle cell to cause the muscle fibers to contract together. the next Examples, the gastrointestinal tract, bile ducts, ureters, uterus, blood vessels CONTRACTILE MECHANISM IN SMOOTH MUSCLE Chemical Basis for Smooth Muscle Contraction Smooth vs. Striated Muscle ❑Smooth muscle contains both actin and myosin filaments, having chemical characteristics similar to those of the actin and myosin filaments in skeletal muscle. ❑Actin and myosin filaments interact with each other in much the same way that they do in skeletal muscle ❑The contractile process is activated by calcium ions, and adenosine triphosphate (ATP) is degraded to adenosine diphosphate (ADP) to provide the energy for contraction. CONTRACTILE MECHANISM IN SMOOTH MUSCLE Chemical Basis for Smooth Muscle Contraction Smooth vs. Striated Muscle ➢ It does not contain the troponin complex that is required in the control of skeletal muscle contraction, and thus the mechanism for control of contraction is different ➢ major differences The physical organization of smooth muscle Excitation-contraction coupling Control of the contractile process by calcium Duration of contraction The amount of energy required for contraction CONTRACTILE MECHANISM IN SMOOTH MUSCLE Physical Basis for Smooth Muscle Contraction ➢ Smooth muscle does not have the same striated arrangement of actin and myosin filaments as is found in skeletal muscle ➢ Large numbers of actin filaments attached to dense bodies. ➢ This contractile unit is similar to the contractile unit of skeletal muscle, but without the regularity of the skeletal muscle structure; in fact, the dense bodies of smooth muscle serve the same role as the Z disks in skeletal muscle. ❑ In skeletal muscle, overlapping actin and myosin anchored to both the M line and Z-discs by titin, provides structural stability and also contributes to force transmission through the sarcomeres. ➢Most of the myosin filaments have “sidepolar” cross-bridges arranged so that the bridges on one side hinge in one direction and those on the other side hinge in the opposite direction. ➢This configuration allows the myosin to pull an actin filament in one direction on one side while simultaneously pulling another actin filament in the opposite direction on the other side. Smooth muscle myosin has hinged heads all along its length. Myosin filament Actin filament Figure 12.25b (2 of 2) Comparison of Smooth Muscle Contraction and Skeletal Muscle Contraction 1. Slow Cycling of the Myosin Cross-Bridges 2. Low Energy Requirement to Sustain Smooth Muscle Contraction • Slowness of attachment and detachment of the cross-bridges • Cross-bridge heads have far less ATPase activity than in skeletal muscle • Because of slow attachment and detachment cycling of the cross-bridges • Only one molecule of ATP is required for each cycle • Sustainability for the intestines • urinary bladder • Gallbladder and other viscera maintain tonic muscle contraction 3. Slowness of Onset of Contraction and Relaxation of the Total Smooth Muscle Tissue • Caused by the slowness of attachment and detachment of the cross-bridges with the actin filaments. • The initiation of contraction in response to calcium ions is much slower than in skeletal muscle 4. The Maximum Force of Contraction Is Often Greater in Smooth Muscle Than in Skeletal Muscle 5. The “Latch” Mechanism Facilitates Prolonged Holding of Contractions of Smooth Muscle 6. Stress-Relaxation of Smooth Muscle Results from the prolonged period of attachment of the myosin cross-bridges to the actin filaments. • It can maintain prolonged tonic contraction with little use of energy. • Little continued excitatory signal is required from nerve fibers or hormonal sources • Seen in visceral unitary type of smooth muscle of many hollow organs • Ability to return to nearly its original force of contraction seconds or minutes after it has been elongated or shortened • Except for short periods, they allow maintain about the same amount of pressure inside its lumen despite sustained, large changes in volume. REGULATION OF CONTRACTION BY CALCIUM IONS • The initiating stimulus for most smooth muscle contraction is an increase in intracellular calcium ions. This increase can be caused in different types of smooth muscle by ➢Nerve stimulation of the smooth muscle fiber ➢Hormonal stimulation ➢Stretch of the fiber ➢Change in the chemical environment of the fiber Smooth muscle contraction is activated by an entirely different mechanism • Smooth muscle does not contain troponin • Neuromuscular junctions do not occur in smooth muscle • No regular motor plate (like in skeletal muscle) • Not arranged in orderely sarcomers • Ordered diagonally • No regular pattern of overlap • Varicosities are present • Instead, the autonomic nerve fibers that innervate smooth muscle generally branch diffusely on top of a sheet of muscle fibers In place of troponin, smooth muscle cells contain a large amount of another regulatory protein called calmodulin Intracellular calcium ion (Ca++ ) concentration increases when Ca++ enters the cell through calcium channels in the cell membrane or is released from the sarcoplasmic reticulum. The Ca++ binds to calmodulin (CaM) to form a Ca++ -CaM complex, which then activates myosin light chain kinase (MLCK). The active MLCK phosphorylates the myosin light chain leading to attachment of the myosin head with the actin filament and contraction of the smooth muscle. ADP, adenosine diphosphate; ATP, adenosine triphosphate; P, phosphate. Source of Calcium Ions That Cause Contraction ❑ An important difference is that the sarcoplasmic reticulum, which provides virtually all the calcium ions for skeletal muscle contraction, is only slightly developed in most smooth muscle ❑ Instead, most of the calcium ions that cause contraction enter the muscle cell from the extracellular fluid at the time of the action potential or other stimulus. ❑ That is, the concentration of calcium ions in the extracellular fluid is greater than 10−3 molar, in comparison with less than 10−7 molar inside the smooth muscle cell; this situation causes rapid diffusion of the calcium ions into the cell from the extracellular fluid when the calcium channels open. Role of the Smooth Muscle Sarcoplasmic Reticulum Figure 8.4 shows a few slightly developed sarcoplasmic tubules that lie near the cell membrane in some larger smooth muscle cells. • Small invaginations of the cell membrane, called caveolae, abut the surfaces of these tubules. • CAVEOLA instead of T-TUBULES in skeletal muscles • The caveolae suggest a rudimentary analog of the transverse tubule system of skeletal muscle Smooth Muscle Contraction Is Dependent on Extracellular Calcium Ion Concentration. ➢ When the extracellular fluid calcium ion concentration decreases smooth muscle contraction usually ceases. ➢ Therefore, the force of contraction of smooth muscle is usually highly dependent on the extracellular fluid calcium ion concentration. ❑ Relaxation of smooth muscle occurs when calcium ion (Ca++ ) concentration decreases below a critical level as Ca++ is pumped out of the cell or into the sarcoplasmic reticulum. ❑ Ca++ is then released from calmodulin (CaM) and myosin phosphatase removes phosphate from the myosin light chain, causing detachment of the myosin head from the actin filament and relaxation of the smooth muscle. This pump requires ATP and is slow acting in comparison with the fast-acting sarcoplasmic reticulum pump in skeletal muscle. Therefore, a single smooth muscle contraction often lasts for seconds rather than hundredths to tenths of a second, as occurs for skeletal muscle. Myosin Phosphatase Is Important in Cessation of Contraction. ➢ Relaxation of the smooth muscle occurs when the calcium channels close and the calcium pump transports calcium ions out of the cytosolic fluid of the cell. When the calcium ion concentration falls below a critical level, the aforementioned processes automatically reverse, except for the phosphorylation of the myosin head. Reversal of this situation requires another enzyme, myosin phosphatase located in the cytosol of the smooth muscle cell, which splits the phosphate from the regulatory light chain. Then the cycling stops and contraction ceases. The time required for relaxation of muscle contraction, therefore, is determined to a great extent by the amount of active myosin phosphatase in the cell. MEMBRANE POTENTIALS AND ACTION POTENTIALS IN SMOOTH MUSCLE The action potentials of visceral smooth muscle occur in one of two forms: (1) spike potentials or (2) action potentials with plateaus 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. Spike Potentials. Typical spike action potentials, such as those seen in skeletal muscle, occur in most types of unitary smooth muscle. 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 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 without an extrinsic stimulus. ➢ This activity is often associated with a basic slow wave rhythm of the membrane potential. Calcium Channels Are Important in Generating the Smooth Muscle Action Potential. ▪ The smooth muscle cell membrane has far more voltage-gated calcium channels than does skeletal muscle but few voltage-gated sodium channels. Therefore, sodium participates little in the generation of the action potential in most smooth muscle. This flow occurs in the same self-regenerative way as occurs for the sodium channels in nerve fibers and in skeletal muscle fibers. However, the calcium channels open many times more slowly than do sodium channels, and they also remain open much longer. These characteristics largely account for the prolonged plateau action potentials of some smooth muscle fibers. Another important feature of calcium ion entry into the cells during the action potential is that the calcium ions act directly on the smooth muscle contractile mechanism to cause contraction. Thus, the calcium performs two tasks at once. Slow Wave Potentials in Unitary Smooth Muscle Can Lead to Spontaneous Generation of Action Potentials. The slow wave itself is not the action potential. That is, it is not a selfregenerative process that spreads progressively over the membranes of the muscle fibers. Instead, it is a local property of the smooth muscle fibers that make up the muscle mass. The cause of the slow wave rhythm is unknown. 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. However, when the peak of the negative slow wave potential inside the cell membrane rises in the positive direction from −60 to about −35 millivolts (the approximate threshold for eliciting action potentials in most visceral smooth muscle), an action potential develops and spreads over the muscle mass and contraction occurs. Figure 8-7B demonstrates this effect, showing that at each peak of the slow wave, one or more action potentials occur These repetitive sequences of action potentials elicit rhythmical contraction of the smooth muscle mass. Therefore, the slow waves are called pacemaker waves. this type of pacemaker activity controls the rhythmical contractions of the gut. Effect of Local Tissue Factors and Hormones to Cause Smooth Muscle Contraction Without Action Potentials Approximately half of all smooth muscle contraction is likely initiated by stimulatory factors acting directly on the smooth muscle contractile machinery and without action potentials. Two types of non-nervous and nonaction potential stimulating factors often involved are (1) local tissue chemical factors (2) various hormones ❑ Action potentials usually do not develop because the fibers are too small to generate an action potential. ❑ In small smooth muscle cells, even without an action potential, the local depolarization (called the junctional potential) caused by the nerve transmitter substance itself spreads “electrotonically” over the entire fiber Effects of Hormones on Smooth Muscle Contraction Among the more important of these hormones are norepinephrine, epinephrine, angiotensin II, endothelin, vasopressin, oxytocin, serotonin, and histamine. ❖ Smooth muscles have considerable diversity in how they initiate contraction or relaxation in response to different hormones, neurotransmitters, and other substances. ❖ In some instances, the same substance may cause either relaxation or contraction of smooth muscles in different locations. For example, norepinephrine inhibits contraction of smooth muscle in the intestine but stimulates contraction of smooth muscle in blood vessels. Disruption of PDGFRalpha signaling disturbs the growth of dental cusp and interferes with the critical extension of palatal shelf during craniofacial development. Andrae J. et al. 2008 Smooth Muscle • Contracts and relaxes much more slowly • Uses less energy • Sustains contractions for extended periods Figure 12.24 Duration of Muscle Twitch in the Three Types of Muscle Smooth muscles are the slowest to contract and to relax. Skeletal Smooth Tension Cardiac 0 1 2 Time (sec) 3 4 5