Skeletal Muscle Contraction 5/11/2017 Dr. Hiwa Shafiq Skeletal Muscle Fiber About 40 per cent of the body is skeletal muscle, and 10 per cent is smooth and cardiac muscle. Skeletal muscles are composed of numerous fibers and each fibers is made up of successively smaller subunits. In most skeletal muscles, each fiber extends the entire length of the muscle. Except for about 2 per cent of the fibers, each fiber is usually innervated by only one nerve ending, located near the middle of the fiber. The cell membrane of the muscle fiber is called sarcolemma and the cytoplasm is called sarcoplasm. The sarcoplasmic reticulum is the endoplasmic reticulum of muscle fiber extremely important in muscle contraction. 1
Each muscle fiber consist of myofibrils (1500 myosin filaments and 3000 actin filaments) responsible for the actual muscle contraction. Myosin and actin filaments partially interdigitate causing myofibrils to have alternate light and dark bands (I bands and A bands) (striated appearance). The small projections from the sides of the myosin are called cross-bridges. It is the interaction between these cross-bridges and the actin filaments that causes contraction 2
From the Z discs, actin filaments extend in both direction to interdigitate with the myosin. The portion of the myofibril that lies between two successive Z discs is called a sarcomere. The sarcomere shortens during muscle contraction to a degree that the actin filaments completely overlap the myosin filaments. An action potential travels along a motor nerve to its endings on muscle fibers causing secretion of a small amount of acetylcholine After a fraction of a second, the calcium ions are pumped back into the sarcoplasmic reticulum by a Ca++ membrane pump causing muscle contraction to cease. The calcium ions initiate attractive forces between the actin and myosin filaments, causing them to slide alongside each other Steps of skeletal muscle contraction The acetylcholine opens acetylcholine-gated Na channels Large quantities of sodium ions diffuse to the interior raising the negative potential inside muscle membrane and initiating an AP The AP causes the sarcoplasmic reticulum to release large quantities of calcium ions The action potential travels along the muscle fiber 3
Sliding filament 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. 4
Sources of energy for muscle contraction Most of energy during muscle contraction is required to provide walk-along mechanism by which the cross-bridges pull the actin filaments. Some energy is also required for: 1- Pumping calcium ions from the sarcoplasm into the sarcoplasmic reticulum after the contraction is over. 2- Pumping sodium and potassium ions through the muscle fiber membrane to maintain appropriate ionic environment. The concentration of ATP in the muscle fiber is sufficient to maintain full contraction for only 1 to 2 seconds.. 2. Phosphocreatine source The combined energy of both the stored ATP and the phosphocreatine in the muscle is capable of causing maximal muscle contraction for only 5 to 8 seconds. 1. Glycolysis of glycogen This can occur in the absence of oxygen and is about 2.5 times as rapid as ATP formation than oxidative source, but it can only sustain maximum muscle contraction for about 1 minute. 3. Oxidative metabolism. Combining oxygen with the end products of glycolysis and with carbohydrates, fats, and protein to liberate ATP. More than 95 per cent of all energy used by the muscles for sustained, long-term (many hours) contraction is derived from this source. Sources of rephosphorylation 5
Excitation of skeletal muscle The Neuromuscular junction The skeletal muscle fibers are innervated by large, myelinated nerve fibers and each nerve ending makes a junction, called the neuromuscular junction, with the muscle fiber near its midpoint. Both the nerve terminals with muscle fiber plasma membrane together are called the motor end plate. When a nerve impulse reaches the neuromuscular junction, about 125 vesicles of acetylcholine are released from the terminals into the synaptic space (synaptic cleft). The acetylcholine in turn excites the muscle fiber membrane. 6
Different views of the motor end plate. From Guyton and Hall TB 11/5/2017 When an action potential spreads over the terminal, calcium channels open and allow calcium ions to diffuse from the synaptic space to the interior of the nerve terminal causing fusion of Ach vesicles and Ach release by exocytosis. When acetylcholine is emptied into the synaptic space, they bind to their receptor on the Ach-gated channels and thus opening the channel. After remaining for a few milliseconds in the synaptic space, the Ach is rapidly destroyed by the enzyme acetylcholinesterase to prevent continued muscle reexcitation. 7
The principal effect of opening the acetylcholine-gated channels: End plate potential then to AP Release of acetylcholine from synaptic vesicles at the NMJ. G and H text book. Excitation-Contraction Coupling Transmission of action potential to the deeper region of the muscle fiber occurs along transverse tubules (T tubules) that penetrate all the way through the muscle fiber from one side of the fiber to the other. The T-tubules communicate with the extracellular fluid surrounding the muscle fiber, and they contain extracellular fluid in their lumens. When an action potential spreads over a muscle fiber membrane, a potential change also spreads along the T tubules to the deep interior of the muscle fiber. 8
The T tubule action potentials cause release of calcium ions inside the muscle fiber and these calcium ions then cause contraction. This overall process is called excitationcontraction coupling. Then the Ca ions are pumped back into the sarcoplasmic reticulum. 9
Smooth muscle 10
Smooth muscle composed of fibers that are both shorter and smaller than that of skeletal muscle. There are two major types of smooth muscles: 1. Multi-unitsmooth muscle. 2. Single-unit (unitary) smooth muscle. Multi-unit smooth muscle Composed of discrete, separate smooth muscle fibers that operate independently of the other fibers. Often innervated by a single nerve ending. Controlled by nervous signal. Examples: Ciliary and iris muscles of the eye and piloerector muscle of the hair. Single unit smooth muscle Arranged in a mass of hundreds to thousands of smooth muscle fibers that contract together as a single unit. The muscle cell membranes are adherent to one another 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 so that action potentials can travel from one fiber to the next and cause the muscle fibers to contract together. They are called syncytial or visceral smooth muscle, and are found in the walls of most viscera. 11
Contraction of smooth muscle Chemical basis for smooth muscle contraction is similar to that of the skeletal muscle (i.e it contains both actin and myosin filaments). Physical basis for smooth muscle contraction is different from that of the skeletal muscle in the following way: 12
They do not have the same striated arrangement of actin and myosin filaments. Actin filaments are attached to the dense bodies which are attached to the cell membrane. Dense bodies of adjacent cells membrane are bonded together by intercellular protein bridges which permit transmission of contractile force from one cell to the other. There are usually 5 to 10 times as many actin filaments as myosin filaments. 13
Comparison of smooth muscle and skeletal muscle contraction Slowness of Onset of Contraction and Relaxation of the Total Smooth Muscle Tissue. A typical smooth muscle requires a total contraction time of 1 to 3 seconds. Slow Cycling of the Myosin Cross-Bridges. Attachment of myosin cross-bridges to actin, then release from the actin, and reattachment for the next cycle is much, much slower in smooth muscle than in skeletal muscle. Energy Required 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. Force of Muscle Contraction. It is much greater in the smooth muscle than the skeletal muscle. Control of smooth muscle contraction Unlike skeletal muscles, smooth muscles can be stimulated to contract by multiple types of signals: Nervous signals Hormonal stimulation Stretch of the muscle Change in the chemical environment of the fiber. 14
The vesicles of the autonomic nerve fiber endings contain acetylcholine in some fibers and norepinephrine in others, but they are never secreted by the same nerve fibers. Acetylcholine is an excitatory transmitter substance in some organs but an inhibitory transmitter in other organs. When acetylcholine excites a muscle fiber, norepinephrine ordinarily inhibits it. Conversely, when acetylcholine inhibits a fiber, norepinephrine usually excites it. 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. Membrane Potentials and Action Potentials in Smooth Muscle The intracellular potential of a smooth muscle fiber is usually about -50 to -60 millivolts. The action potentials of visceral smooth muscle (unitary smooth muscle) occur in one of two forms: (1) Spike potentials (similar to those of skeletal muscle) (2) Action potentials with plateaus. Here after the spike potential, the repolarization is delayed for several hundred to as much as 1000 milliseconds (1 second). This accounts for the prolonged contraction that occurs in some types of smooth muscle, such as ureter and uterus. 15
Typical spike potential Repeated spike potential elicited by slow rhythmical waves in the intestinal wall Action potential with plateau in the uterus Smooth Muscle Contraction in Response to Local Tissue Chemical Factors: 1. Lack of oxygen in the local tissues causes smooth muscle relaxation and, therefore, vasodilatation. 2. Excess carbon dioxide causes vasodilatation. 3. Increased hydrogen ion concentration causes vasodilatation. 16
Effects of Hormones on Smooth Muscle Contraction. Most circulating hormones in the blood affect smooth muscle contraction to some degree, and some have profound effects. Among the more important of these are norepinephrine, epinephrine, acetylcholine, angiotensin, endothelin, vasopressin, oxytocin, serotonin, and histamine. 17