Smooth Muscle Contraction PDF

Peripheral Nervous System The PNS is subdivided into the 1. somatic system. 2. autonomic system. The peripheral nervous system (PNS) lies outside the central nervous system and is composed of nerves and ganglia. ✓Nerves are bundles of myelinated axons. ✓ Ganglia (sing., ganglion) are swelling...

Peripheral Nervous System The PNS is subdivided into the 1. somatic system. 2. autonomic system. The peripheral nervous system (PNS) lies outside the central nervous system and is composed of nerves and ganglia. ✓Nerves are bundles of myelinated axons. ✓ Ganglia (sing., ganglion) are swellings associated with nerves that contain collections of cell bodies. The somatic system: serves the skin, skeletal muscles, and tendons. About 40 per cent of the body is skeletal muscle, and perhaps another 10 per cent is smooth and cardiac muscle. For voluntary muscles, all contraction (excluding reflexes) occurs as a result of conscious effort originating in the brain. The brain sends signals, in the form of action potentials, through the nervous system to the motor neuron that innervates several muscle fibers. In the case of some reflexes, the signal to contract can originate in the spinal cord through a feedback loop with the grey matter. Type of skeletal muscle fiber ✓ The muscle of the body is composed of a mixture of so-called fast fiber which is react rabidly, and slow muscle fibers is react slowly, another type of fibers gradated between these two extremes. Fast fiber Slow fiber Size of fiber large small Sarcoplasmic Big small reticulum Blood vessels less amount extra amount Energy Glycolytic oxidative enzyme enzyme Mitochondria Few number Large number Myoglobin small amount Large- amount Muscle Hypertrophy and Muscle Atrophy When the total mass of a muscle increases, this is called muscle hypertrophy. When it decreases, the process is called muscle atrophy. Rigor Mortis Several hours after death, all the muscles of the body go into a state of contracture called “rigor mortis”; that is,the muscles contract and become rigid, even without action potentials. This rigidity results from loss of all the ATP. The muscles remain in rigor until the muscle proteins deteriorate about 15 to 25 hours later  In the body, muscles are innervated to contract by nerves, each axon within a nerve stimulates a number of muscle fibers. A nerve fiber together with all of the muscle fibers it innervates is called a motor unit. A motor unit obeys the all-or-none law. Why? Because all the muscle fibers in a motor unit are stimulated at once, and they all either contract or do not contract. A variable of interest is the number of muscle fibers within a motor unit. For example, in the ocular muscles that move the eyes, the innervation ratio is one motor axon per 23 muscle fibers, while in the gastrocnemius muscle of the lower leg, the ratio is about one motor axon per 1,000 muscle fibers.  The skeletal muscle fibers are innervated by large, myelinated nerve fibers that originate from large motoneurons in the anterior horns of the spinal cord. Each nerve ending makes a junction, called the neuromuscular junction Physiologic Anatomy of the Neuromuscular Junction The nerve fiber forms a complex of branching nerve terminals that invaginate into the surface of the muscle fiber but lie outside the muscle fiber plasma membrane. The invaginated membrane is called the synaptic gutter The space between the synaptic gutter and the fiber membrane is called the synaptic space or synaptic cleft.  At the bottom of the gutter are numerous smaller folds of the muscle membrane called subneural clefts, which greatly increase the surface area at which the synaptic transmitter can act. In the axon terminal are many mitochondria that supply adenosine triphosphate (ATP), the energy source that is used for synthesis of an excitatory transmitter acetylcholine The presynaptic axons form bulges called terminal buttons which, have active zones that contain vesicles, full of acetylcholine molecules. These vesicles can fuse with the presynaptic membrane and release ACh molecules into the synaptic cleft via exocytosis after depolarization. Effect of Acetylcholine on the Postsynaptic Muscle Fiber Membrane to Open Ion Channels Ach receptors is allow the important positive ions— sodium Na++ , potassium K+ and calcium Ca++ to move easily through the opening. Conversely, negative ions, such as chloride ions, do not pass through because of strong negative charges in the mouth of the channel that repel these negative ions The short time that the acetylcholine remains in the synaptic space—a few milliseconds at most— normally is sufficient to excite the muscle fiber. Fatigue of the neuromuscular junction Stimulation of the nerve fiber at rates greater than 100 times per second for several minutes often diminishes the number of acetylcholine vesicles so much that impulses fail to pass into the muscle. This is called fatigue of the neuromuscular junction, and it is the same effect that causes fatigue of synapses in the central nervous system when the synapses are overexcited. Physiologic Anatomy of Skeletal Muscle Sarcolemma is the cell membrane of the muscle fiber. Myofibrils; Actin and Myosin Filaments. Each muscle fiber contains several hundred to several thousand myofibrils (the light bands contain only actin filaments and the dark bands contain myosin filaments, ) ends of the actin filaments are attached to a so-called Z disc The Z disc, which itself is composed of filamentous proteins different from the actin and myosin filaments Titin Filamentous Molecules act as a framework that holds the myosin and actin filaments in place so that the contractile machinery of the sarcomere will work The portion of the myofibril (or of the whole muscle fiber) that lies between two successive Z discs is called a sarcomere  Sarcoplasm: many myofibrils of each muscle fiber are suspended side by side in the muscle fiber. The spaces between the myofibrils are filled with intracellular fluid called sarcoplasm Sarcoplasmic Reticulum: in the sarcoplasm surrounding the myofibrils of each muscle fiber is an extensive reticulum, called the sarcoplasmic reticulum. Molecular Mechanism of Muscle Contraction In the relaxed state, the ends of the actin filaments extending from two successive Z discs barely begin to overlap one another. Conversely, in the contracted state, these actin filaments have been pulled inward among the myosin filaments, so that their ends overlap one another to their maximum extent. Also, the Z discs have been pulled by the actin filaments up to the ends of the myosin filaments. Thus, muscle contraction occurs by a sliding filament mechanism. Molecular Characteristics of the Contractile Filaments Actin Filament is also complex. It is composed of three protein components: (1) actin, (2)tropomyosin, (3) and troponin. Actin Molecules: in the actin molecules there is many molecules of ADP. It is believed that these ADP molecules are the active sites on the actin filaments with which the crossbridges of the myosin filaments interact to cause muscle contraction. Tropomyosin Molecules. These molecules are wrapped spirally around the sides of the actin. In the resting state, the tropomyosin molecules lie on top of the active sites of the actin strands, so that attraction cannot occur between the actin and myosin filaments to cause contraction.  Troponin: These are actually complexes of three loosely bound protein subunits, each of which plays a specific role in controlling muscle contraction. Troponin I :has a strong affinity for actin. Troponin T: has a strong affinity for tropomyosin Troponin C: has a strong affinity for calcium ions. The myosin filament is composed of two heavy chains (tail), and light Chains (head). But what causes the actin filaments to slide inward among the myosin filaments? This is caused by forces generated by interaction of the cross-bridges from the myosin filaments with the actin filaments. Mechanism of muscle contraction The initiation and execution of muscle contraction occur in the following sequential steps. 1. An action potential travels along a motor nerve to its endings on muscle fibers. At each ending, the nerve secretes a small amount of the neurotransmitter substance acetylcholine. Opening of the acetylcholine-gated channels allows large quantities of sodium ions to diffuse to the interior of the muscle fiber membrane. This initiates an action potential at the membrane. 2. The action potential travels along the muscle fiber membrane through the T tubules. Here it causes the sarcoplasmic reticulum to release large quantities of calcium ions (calsequestrin) 3. The calcium ions initiate attractive forces between the actin and myosin filaments, causing them to slide alongside each other, which is the contractile process. 4. After a fraction of a second, the calcium ions are pumped back into the sarcoplasmic reticulum by a Ca++ membrane pump, and they remain stored in the reticulum until a new muscle action potential comes along; this removal of calcium ions from the myofibrils causes the muscle contraction to cease 5. Arrival of the AP at the sarcoplasmic reticulum leads to opening of Ca+ channels on its membrane , consequently Ca+ diffuses out into the cell cytoplasm and combines with tropionin. This makes tropionin pull tropomyosin sideway, thereby exposing the active sites on actin. 6. As soon as the actin filament becomes activated by the calcium ions, the heads of the cross-bridges from the myosin filaments become attracted to the active sites of the actin filament, and this, in some way, causes contraction to occur. The energy liberated is used for movement of cross bridges so that these filaments slide upon each other, bringing the Z lines closer and making sarcomer shorter Contraction and Excitation of Smooth Muscle  The smooth muscle, which is composed of far smaller myofibers usually 1 to 5 micrometers in diameter and only 20 to 500 micrometers in length. In contrast, skeletal muscle fibers are as much as 30 times greater in diameter and hundreds of times as long. Smooth muscle can generally be divided into two major types, ✓Multi-Unit Smooth Muscle: separate smooth muscle fibers, each fiber operates independently of the others and often is innervated by a single nerve ending. Some examples of multi-unit smooth muscle are the ciliary muscle and iris muscle of the eye, the piloerector muscles of skin, bronchiole of the lung. ✓Unitary Smooth Muscle: a mass of hundreds to thousands of smooth muscle fibers that contract together as a single unit (syncytial smooth muscle, visceral smooth muscle ), the cell membranes are joined by many gap junctions. Some example in the trachea, visceral organs, lines blood vessels (except large elastic arteries), the urinary tract, and the digestive tract. Physical Basis for Smooth Muscle Contraction Smooth muscle contains both actin and myosin filaments, but it does not have the same striated arrangement of actin and myosin filaments. There are a large numbers of actin filaments attached to so-called dense bodies. Some of these bodies are attached to the cell membrane. There is another difference, most of the myosin filaments have what are called “sidepolar” cross-bridges arranged Chemical Basis for Smooth Muscle Contraction The contractile process is activated by calcium ions, and adenosine triphosphate (ATP) is degraded to adenosine diphosphate (ADP) to provide the energy for contraction. ✓Unlike skeletal muscle, smooth muscle is dependent on two sources of calcium in order to initiate contraction. These two sources are: 1. The S.R. of the smooth muscle cell does not contain enough Ca+ 2. Extracellular calcium that can enter the smooth muscle cell via calcium channels on the membrane of the smooth muscle cell. Neuromuscular Junctions of Smooth Muscle The autonomic nerve fibers that innervate smooth muscle generally branch diffusely on top of a sheet of muscle fibers. The axons that innervate smooth muscle fibers do not have typical branching end feet of the type in the motor end plate on skeletal muscle fibers. Instead, form so called diffuse junction. Characteristics Smooth muscle Skeletal muscle Appearance of muscle Smooth with no Striated with troponin troponin and less and more myosin myosin Sarcomeres Un regular with dense Regular with z line body Length of contractile sarcomere 80% 30% Source of Ca ICF ICF and ECF Cross bridges Have less ATPase Have more ATPase Cycling of the Myosin Cross-Bridges Slow 1/10 to 1/300 fast Energy Required to Sustain Less as 1/10 to 1/300 More 10 to 300 contraction Time contraction and Relaxation of 0.2 to 30 seconds 0.03 to 0.1 seconds the muscle Force of Muscle Contraction 4 to 6 Kg/cm 3 to 4 Kg/cm Resting potential -50 to - 60 -80 to -90 The stimulus Nerve, hormone, nerve chemical Regulatory protein Calmodulin Troponin Since smooth muscle cells have little voltage-gated sodium channels, the action potential generated is the result of the calcium influx. Unlike skeletal muscle, smooth muscle uses second messenger systems to open the calcium channels on the S.R. due to the release of a neurotransmitter The protein-ligand binding (Gq protein) is usually a molecule found in the smooth muscle which it is binding to a neurotransmitter such as Epinephrine, and Ach, and lead to the production of inosital triphosphate (IP3). The IP3 is then directly responsible for opening the calcium channels on the S.R. membrane, allowing the calcium to enter the cytoplasm of the cell  Smooth Muscle Contraction ✓In place of troponin, smooth muscle cells contain a large amount of another regulatory protein called calmodulin. ✓The calcium ions bind with calmodulin. The calmodulin-calcium combination joins with and activates myosin kinase, a phosphorylating enzyme. ✓ One of the light chains of each myosin head, called the regulatory chain, becomes phosphorylated in response to this myosin kinas ✓ The head has the capability of binding with the actin filament and proceeding through the entire cycling process “pulls,” the same as occurs for skeletal muscle, thus causing muscle contraction. Cessation of Contraction When the calcium ion concentration falls below a critical level, contraction processes automatically reverse, except for the phosphorylation of the myosin head. Reversal of this requires phosphorelase enzyme, which splits the phosphate from the regulatory light chain. Then the cycling stops and contraction ceases