Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
147029604 Physiology of Nerve and Muscle I. Nerve Nerve cell is called neuron. There are 100 billion neurons (give or take 100 million) differ based on their structure, chemistry and function. Neurons confer the unique functions of the nervous system. Glia are the supporting elements which are 10 times as many as neurons. Neurons contain the same basic structures as most other cells; Cell body (soma or perikaryon) and neurites (axons and dendrites). Cell body usually gives rise to a single axon which conducts nerve impulse from one neuron to the next. It is up to 1 meter in length. The speed of the nerve impulse is a function of the diameter of the axon. Dendrites are small (rarely more than 2mm) and organized symmetrically (antennae). The term dendritic tree is a collective term for all neurites of a given neuron. Neural signals are either efferent (away from the cell body) or afferent (towards the cell body). Fig: 1 -1- 147029604 1. Types of glia in CNS: a. Astrocytes: Most abundant, most versatile. Their numerous processes cling to neurons and their synaptic endings, and cover nearby capillaries. So they support and brace the neurons and anchor them to the nutrient supply lines. They have a role in making exchange between capillaries and neurons, in helping determine of capillary permeability, guiding migration of young neurons and in synapse formation. Regulate extracellular space, mopping up leaked potassium ions, restricting and recycling neurotransmitters. They are connected to each other by gap junctions and signal each other both by taking in calcium (calcium pulse or calcium sparks) and by releasing extracellular messengers. Recently it is found that astrocytes participate in information processing in the brain Fig: 2 b. Microglia: Migrate toward injured or troubled neurons and transform into special type of macrophages. So they are the scavenger cells that get rid of microorganisms or neural debris. c. Ependymal cells: Line the central cavities of brain and spinal cord. d. Oligodendrocytes: Myelinating glia in central neurons that form myelin sheath (what holds a sword) which wrap around the axons to function in insulation. -2- 147029604 Fig. 3: 2. Types of glia in PNS: a. Schwann Cells: Produce myelin sheath and neurilemma in peripheral neurons. In addition to insulation, they aid in regeneration of damaged peripheral nerve fibers. b. Satellite cells: Surround cell bodies in PNS and have many of the same functions as astrocytes in CNS. Fig. 4 -3- 147029604 Classification of nerves 1. Physioanatomic classification: Neurons are classified into afferent (sensory) and efferent (motor). Each is subdivided into somatic and visceral neurons. The latter subdivisions are further subdivided into general and special neurons. 2. Another classification is according to conduction velocity and caliber of nerve fiber. From larger to lower caliber they are: Nerve type Aα has the largest diameter and fastest conduction velocity e.g. somatic motor and proprioceptive nerve fibers. Nerve type Aβ e.g. sensory fibers of fine touch and fine pressure. Nerve type Aγ e.g. motor fibers to muscle spindle. Nerve type Aδ e.g. sensory fibers of acute pain, crude touch and cold. Nerve type B e.g. preganglionic autonomic nerve fibers. Nerve type C has the smallest diameter unmyelinated fibers e.g. sensory fibers of chronic pain, heat, gross pressure and postganglionic sympathetic fibers. Resting membrane potential All living cells (whether animal or plant cells) exhibit potential difference across their plasma membranes when microelectrodes are inserted into these cells where the membrane interior is negative in relation to the membrane exterior. This is called resting membrane potential (RMP) and it is due to uneven distribution of ions inside and outside the membrane. Ion Extracellular Intracellular Na+ K+ Cl– Phosphates Proteins 142 mEq/L 4 mEq/L 103 mEq/L 4 mEq/L 30 mg/dL 10 mEq/L 140 mEq/L 4 mEq/L 75 mEq/L 200 mg/dL Accordingly, RMP of nerve cell is –70 mV, RMP of skeletal muscle is –90 mV, RMP of cardiac muscle is –85 mV, and lastly RMP of smooth muscle is variable but nearly about –50 mV. -4- 147029604 The following ionic fluxes are responsible for the electric phenomenon of resting membrane potential: 1. Sodium-Potassium pump: This is called Na+-K+ ATPase pump which extrudes three sodium ions outside the cell and intrudes two potassium ions inside. This results in much positive ions outside plasma membrane. 2. Sodium channels are inactive at rest. They are voltage gated channels i.e. they are activated by electric current. This means that sodium influx is not possible unless membrane potential is changed from resting to action potential. 3. Potassium channels allow continuous passive diffusion of K+ outside the cell due to concentration gradient. This K+ efflux results in diffusion potential and increased positive charges outside plasma membrane which is the major factor responsible for resting membrane potential. 4. Chloride ions stand still inside the cell due to their higher concentration outside the cell. This conserves negative charges inside plasma membrane. 5. Anionic proteins and phosphates can not leave the cell due to their large size making plasma membrane impermeable to their efflux. This adds to the negativity of plasma membrane interior. Fig. 5 PROTEINS¯ 3Na PHOSPHATES¯ CHLORIDE¯ + Pump 2K+ K+ -5- 147029604 Local responses and action potential Nerve and muscle cells are excitable cells i.e. they have the ability to reverse the negativity of their membrane potential in response to a sufficient external stimulus. The external stimulus may be electrical, chemical, physical or other types of stimuli. This change in membrane potential is called action potential. The response in nerve cell is transmission of action potential (nerve impulse) while the response in muscle cell is contraction. Fig. 6: Curves of local responses and action potential in neuron Overshoot of depolarization Repolarization Depolarization RMP Threshold ↑↑L o c a l ↑↑ r e s p o n s e s ↑↑ Hyperpolarization Weak external stimuli when applied to the neuron may cause local responses which may increase or decrease with the charge and amplitude of stimuli and the responses subside after removal of these stimuli. Local responses may be cathodal (+ve) or anodal (-ve). Catelectrotonic stimuli cause less negative membrane potential, while anelectrotonic stimuli cause more negative membrane potential. When a sufficient stimulus raises the membrane potential 15 mV above RMP (i.e. from –70 mV to –55 mV); action potential phases will start and does not stop until complete cycle occurs. This is called all-or-none rule. The membrane potential at which action potential starts is called threshold potential or firing potential. Subthreshold stimuli may not affect the membrane potential or cause only local responses while supramaximal stimuli induce the same effects as threshold stimuli and do not change the shape of action potential curve. -6- 147029604 The phases of action potential curve in neurons are: 1-Depolarization phase: Sharp rise of curve toward zero membrane potential which overshoots to reach about +35 mV. This phase is due to activation of all fast Na+ channels with inrush of huge number of Na+ ions causing plasma membrane to lose its negativity. 2-Repolarization phase: Rapid fall of the curve toward the previous negative potential which occurs due to fast inactivation of Na+ channels and continuous pumping of Na+ and passive diffusion of K+ outside the cell. 3-Hyperpolarization phase: Decline of the curve to a more negative potential than RMP which is here about –72 mV and it is due to slow closure of K+ channels. After that, the membrane regains its RMP. Any stimulus, however large, does not induce any new action potential at time of previous depolarization until third repolarization is complete. This is called absolute refractory period because Na+ channels cannot be reactivated immediately after previous activation. From the point of third repolarization to the end of repolarization phase a stronger stimulus is needed to induce new, but weaker, action potential because fewer Na+ channels can be activated. This is called relative refractory period. 1/3 repolarization Relative refractory period Absolute refractory period Depolarization Fig. 7: Full repolarization Threshold Calcium ions stabilize the membrane by increasing threshold potential ﴾toward more positive position﴿ so, lack of Ca++ results in lower threshold potential which makes the membrane very excitable and continuously firing ﴾tetanus﴿. -7- 147029604 Propagation of action potential Action potential is triggered in axon hillock due to presence of large number of Na+ channels and transmitted along the axon. The huge number of positive charges inside the firing segment of membrane will be equilibrated by the adjacent segments resulting in electrotonic flow of current which is very fast (like in the solid electricity wire). Nerve fiber is not a solid wire, instead, it is leaky and surrounded by sea of electrolytes. So, the impulse will gradually subside unless there are new AP waves at the adjacent segments of the axon. Every new wave will cost time (0.1 milliseconds for each AP) which will extremely delay the transmission of impulse. Myelin sheath provides insulation to prevent leakage of ions and, hence, increases conduction velocity. Fig. 8: Electrotonic flow of current Insulation is interrupted at regular intervals by nodes of Ranvier which act as augmentation stations to strengthen the ongoing wave of depolarization by triggering new AP waves because these nodes are rich in Na+ channels. This is called saltatory conduction because it is jumping from node to node (See figure 9). It travels in only one direction from soma to axon terminal (orthodromic conduction) and not in the opposite direction (antidromic conduction) because when action potential leaves certain segment, it cannot return immediately to the same segment that passes an absolute refractory period. So, it proceeds forward to a new resting segment not backward to the recovering refractory segment. -8- 147029604 Fig. 9: Saltatory conduction Synaptic and junctional transmission Synapse is the junction between two neurons. The first is called presynaptic neuron and the other is called postsynaptic neuron. Between them is the synaptic cleft. Fig. 10: Presynaptic N Synaptic cleft Postsynaptic N -9- 147029604 Synapses are either chemical or electrical. Electrical synapses are very rare in adult mammalian nervous system. Gap junction is an example of this type where current flows directly through a specialized protein molecule (connexon). The distance between two sides of membrane is very small (5nM). Chemical synapses are the predominant type of synapses where chemical substances called neurotransmitters (NT) are synthesized and stored in synaptic vesicles. When AP arrives at the axon terminal, it opens voltage gated Ca2+ channels (channels that are opened or closed electrically) and Ca2+ influx will increase intracellular Ca2+ concentrations which attract the synaptic vesicles (full of NT substance) to the presynaptic membrane and signals the NT to be released to the synaptic cleft by exocytosis. Vesicles fuse with the active zones of presynaptic membrane. NT diffuses across the synaptic cleft to bind its specific receptor on the postsynaptic membrane. Several types of neurotransmitters are available and each may have several types and subtypes of receptors. Postsynaptic action depends on the nature of the receptor. After that, NT must be inactivated by degradation, reuptake, diffusion, or bioconversion. - 10 - 147029604 Properties of synapses: 1- One-way conduction from pre- to post-synaptic neurons because post synaptic membrane contains no synaptic vesicles. 2- Synapse is a site of neurotransduction (from electrical to chemical signal). 3- Intercellular chemical messages converted into intracellular signal. Fig. 11: (Ionotropic) (Metabotropic) 4- Synaptic potentials are either excitatory (EPSP) or inhibitory (IPSP). EPSP bring the membrane potential toward threshold (depolarize) i.e. cations in or anions out while IPSP move membrane potential away from threshold (hyperpolarize) i.e. anions in or cations out. 5- EPSP and IPSP are present simultaneously in synaptic cleft. 6- Synaptic potentials are not all-or-none potentials. 7- A period of time (about 0.5 ms) is required for the signal to travel from pre- to post-synaptic neurons which is called synaptic delay. - 11 - 147029604 8- Events are summed over time and space (spatiotemporal summation). Effects may be additive or subtractive. Arrival of impulses from numerous synaptic knobs on the same neuron at the same time is called spatial summation and arrival of multiple successive impulses at the same synaptic knob is called temporal summation. Temporal summation Spatial summation 9- Several presynaptic neurons may converge on single postsynaptic neuron. Convergence 10- Single presynaptic neuron may diverge by its axon and its collaterals into several postsynaptic neurons. Divergence - 12 - 147029604 11- Axon collaterals from postsynaptic neurons may reverberate to the presynaptic neuron(s). Reverberation 12- Occlusion means that the sum of activities of several neurons working together is less than the sum of their activities when they work separately. Works separately on 2 neurons Works separately on 2 neurons Works separately on 2 neurons Total together work on 4 neurons Total: separately work on 6 neurons 13- Several successive EPSP may facilitate the synaptic knob to depolarize while several successive IPSP may inhibit the synaptic knob. 14- Continuous recurrent weak synaptic potentials may cause habituation of postsynaptic neuron which will not respond for similar future stimulations while recurrent strong stimulations accompanied by other weak stimulations may cause sensitization of postsynaptic neuron. - 13 - 147029604 Classification of neurotransmitters Two groups of synaptic transmitters A. Small molecule, rapidly acting transmitters: Class I: Acetylcholine Class II: The amines (adrenaline "epinephrine", noradrenaline "norepinephrine", dopamine, serotonine and histamine). Class III: Amino acids (γ-aminobutyric acid "GABA", glycine, glutamate and aspartate). Class IV: Nitric oxide "NO". B. Neuropeptide, slowly acting transmitters: a- Hypothalamic-releasing hormones. b- Pituitary peptides. c- Peptides that act on gut and brain. d- Peptides from other tissues. Criteria for classification as a neurotransmitter a. Molecule must be synthesized and stored in the presynaptic neuron b. Molecule must be released by the presynaptic neuron upon stimulation c. Application of the neurotransmitter directly to the target cell must be shown to produce the same effects as the response produced by the release of the neurotransmitter from the presynaptic neuron. Many neurons release more than a single neurotransmitter. Neurons that use particular neurotransmitters are accordingly named cholinergic (use acetylcholine), catecholinergic (catecholamines: epinephrine, norepinephrine,..), serotonergic (serotonine), amino acidergic ( amino acids), and so on... - 14 - 147029604 Acetylcholine ACh is the neurotransmitter for neuromuscular junction, preganglionic neurons of the sympathetic and parasympathetic PNS, postganglionic neuron of the parasympathetic PNS and basal forebrain and brain stem complexes. ACh is synthesized from acetyl coenzyme A and choline. The reaction is catalyzed by choline acetyl transferase enzyme (CAT). CAT Acetyl coenzyme A + choline Acetylcholine Acetylcholine is degraded in the synaptic cleft by acetylcholinesterase enzyme (ACE). ACE Acetylcholine choline + acetate ACh receptors are nicotinic receptors (protein complex comprised of 5 subunits: subunits are either alpha or beta) and muscarinic receptors. Nicotinic receptors are present in neuromuscular junction, sympathetic ganglia and many parts of CNS. Muscarinic receptors are present in smooth muscles and glands. - 15 - 147029604 II. Muscle Fig: 12 I. Skeletal muscle: General functions of skeletal muscle are: Movement Maintenance of posture Stabilization of joints Temperature homeostasis It is striated voluntary muscle surrounded by epimysium and composed of fasciculi. Each fasciculus is surrounded by perimysium and composed of muscle fibers (elongated muscle cells). Muscle fibers are separated from each other by endomysium and each muscle fiber is surrounded by sarcolemma (plasma membrane) and composed of sarcoplasm (cytoplasm of muscle cells), myofibrils, multiple nuclei, mitochondria and sarcoplasmic reticulum in addition to other cellular components. Myofibrils are composed of myofilaments (thick and thin contractile elements of skeletal muscle which give the muscle its striation). - 16 - 147029604 The functional unit of skeletal muscle is called sarcomere which is composed of the following compartments: 1. A bands (dark anisotropic bands) composed of myosin thick filaments. 2. I bands (light isotropic bands) composed of parts of actin thin filaments not overlapped by myosin. 3. H band (within A band) visible only in relaxed muscle. 4. M line (bisects H band). 5. Z disc (midline membrane in I band connecting myofibrils together). Sarcomere is region of myofibril between two successive Z discs. Fig: 13 H zone I band A band - 17 - 147029604 Thick filaments: Myosin is rod like tail that terminates in two globular heads. The tail is comprised of heavy meromysin (two interwoven polypeptide chains). The head is comprised of light meromysin. Thin myofilaments: Is comprised of G (globular) actin arranged in double stranded helix and two regulatory proteins which are: 1- Tropomyosin (spirals around actin and blocking myosin head binding sites during relaxed state) 2- Troponin (polypeptide complex). Troponin is composed of three subunits: 1.Troponin C (TnC) binds Ca2+ 2.Troponin T (TnT) binds tropomyosin 3.Troponin I inhibitory protein (TnI) that binds actin Troponin-tropomyosin complex attached to actin filament. Tropomyosin positioned to block myosin binding sites on actin filament. ATP and inactive ATPase bound to myosin head. Sarcolemma continues as inward invaginations of various depths called T tubules which are in close proximity to sarcoplasmic reticulum on either side. This is called sarcotubular system which is of great importance in transmission of the propagated action potential wave along sarcolemma deeply via T tubules resulting in release of Ca2+ from sarcoplasmic reticulum stores to be near the myofibrils. Fig: 14 - 18 - 147029604 Contraction of Skeletal Muscle Sliding filament theory of Contraction (excitation contraction coupling) 1- Nerve impulse (afferent signal) from motor neuron arrives motor end plate (neuromuscular junction) resulting in release of Ach into the synaptic cleft to bind nicotinic receptor on post synaptic membrane which opens Na + channels and generates action potential in sarcolemma. 2- AP propagates along sarcolemma and down T tubules resulting in release of Ca2+ from sarcoplasmic reticulum to the myofibrils. 3- Myosin ATPase is activated and ATP splits resulting in high energy myosin-ADP complex. 4- Ca2+ binds to troponin resulting in changes in molecular shape of troponin. 5- Tropomyosin is removed from binding site of myosin on the actin filament and myosin attaches to actin (actin-myosin cross bridge). 6- Potential energy stored in high-energy configuration is used to pivot myosin head. Myosin head bends as it pulls on actin. 7- ADP and inorganic phosphate are released from myosin. 8- New ATP attached to myosin head and cross bridge simultaneously detaches. Following death, there is no ATP and muscle fibers cannot relax (rigor mortis). If no new impulse, Ca2+ is pumped back into sarcoplasmic reticulum (SR) and relaxation occurs. If Ca2+ present from additional impulse, cycle repeats and myosin head “steps” to next binding site on actin. - 19 - 147029604 - 20 - 147029604 Motor unit Motor unit is a single motor neuron + its collaterals and skeletal muscle fibers they supply. Motor unit could be small in size (few collaterals arise from motor nerve to supply few muscle fibers) or large in size (so numerous collaterals and muscle fibers). Three types of muscle fibers are found: Slow oxidative fibers (slow red) Fast oxidative fibers (fast red) which is very rare in human. Fast glycolytic fibers (fast white) Skeletal muscle is a mixture of these three types of fibers, so there are red muscles and white muscles. Red muscles contain higher percentage of red fibers with few white fibers. They respond slowly with long latency and specialized for posture maintenance. They contain more blood capillaries, more mitochondria and more myoglobin. They are resistant to fatigue and sensitive to hypoxia. White muscles contain higher percentage of white fibers with few red fibers. They respond quickly with short latency and specialized for fine skilled movements. They contain less blood capillaries, less mitochondria and less myoglobin. They are less sensitive to hypoxia and easily fatigued. When nerve supply to a slow fiber is cut and replaced by nerve to a fast fiber; the slow fiber becomes fast! Muscle twitch is the response of a muscle to a single supra-threshold stimulus. Strength of contraction increases with successive stimuli. Muscles that are already contracted, contract further with additional Ca2+. If stimulation is delivered prior to relaxation, contractions are summed. At sufficiently high frequencies, no muscle relaxation occurs and contractions fuse into a smooth, sustained contraction (tetanus). - 21 - 147029604 Fig: 15 Primary mechanism for increasing force of contraction is by recruitment Tetanusof multiple motor units at the same time and by increasing the frequency of AP at each unit. At threshold stimulation, first of muscle contraction occurs. As Summation twitches stimulus intensity is increased, additional motor units are activated. Maximal stimulus is the strongest stimulus that causes increased contraction which is accomplished by increased neural activation. The type of movement whether fine or gross is the function of recruitment of numerous or few motor units respectively. When the required movement is fine and graded; numerous small size motor units must work. When the required movement is gross; few large size motor units can help. Types of contraction Muscle tension is the force of contracting muscle on an object. Load is the reciprocal force exerted by the object. To move a load, muscle tension must be greater than load. There are two types of contraction: Isotonic contraction: Muscle changes in length and moves load. Isometric contraction: Tension increases but the muscle length stays constant. The load is greater than force e.g. maintenance of posture. Most real-life movements involve both isometric and isotonic contraction. Muscle Metabolism ATP is the sole source of energy for contraction. Little ATP is stored but it is regenerated (recycled) rapidly: 1. Direct phosphorylation of ADP by creatine phosphate 2. Anaerobic glycolysis: In the absence of oxygen, glycolytic products (pyruvic acid) are metabolized to lactic acid producing additional small quantities of ATP 3. Aerobic glycolysis: Provides 95% of ATP during light exercise. In presence of oxygen, products of glycolysis are broken down entirely with the generation of significant amounts of ATP. 4. Fatty acids are the major source of energy at rest. - 22 - 147029604 During exercise, extra-amount of oxygen is consumed to remove the excess lactate, replenish ATP and creatine phosphate stores and to replace myoglobin. This is called oxygen debt which is the explanation of pant. Exhaustion is a state of fatigue due to accumulation of lactates from anaerobic pathways resulting in decreased pH which inhibits the necessary reactions for muscle contraction. Length-tension relationships Optimum resting sarcomere length (Lmax) is 2µ - 2.2µ at which maximum tension (To) can be generated. Actin and myosin overlap such that sliding can occur over the entire length of the actin filament. When sarcomere length is more than Lmax; there are less actin-myosin cross bridges and muscle tension is less than To and when sarcomere length is less than Lmax; actin filaments on either side will overlap over each other and muscle tension is also less than To. Abnormal contractions Spasm: A sudden involuntary contraction of short duration. Cramps: Painful spasmodic contraction of muscle fibers. Convulsion: Violent tetanic contraction of entire muscle groups. Fibrillation: Asynchronous contraction of individual muscle fibers resulting in flutter with no effective movement. Tic: Spasmodic twitching common in eyelid and facial muscles. Myalgia: Pain in one or more muscles. Myositis: Inflammation of muscle tissue. Poliomylitis: Viral based destruction of motor neurons in the anterior horn of the spinal cord. Contracture: Abnormal sustained contraction resultant from continuous availability of Ca2+ near myofibrils due to lack of Ca2+ pump back to sarcoplasmic reticulum. - 23 - 147029604 II. Cardiac Muscle It is branched and interdigitated and functions as syncytium due to presence of intercalated discs and gap junctions. Its RMP is about -85 mV and its AP is slow and characterized by presence of plateau. The AP phases are: Phase 0: Depolarization lasts about 2 ms and occurs due activation of all Na+ channels with huge influx of Na+ ions. Phase 1: Initial rapid repolarization occurs due fast inactivation of Na+ channels. Phase 2: Plateau lasts about 200 ms and occurs due to opening of Ca 2+ channels and influx of Ca2+ ions. Phase 3: Late rapid repolarization occurs due to closure of Ca2+ channels. Phase 4: Base line (RMP) mV +20 1 2 0 0 3 _ 85 4 0 Time >200 ms Pacemaker potential: Cardiac muscle contraction is myogenic (originated inside the muscle) not neurogenic (initiated by nerve) and the nerve supply is only regulatory. This due to the presence of specialized conductive tissue in the heart called pacemaker tissue. This tissue has unstable low membrane potential called prepotential or pacemaker potential which declines and depolarizes continuously and steadily (due to slow decrease in K+ efflux) which spreads the impulses all over the heart. Steeper prepotentials result in tachycardia, while lower prepotentials result in bradycardia. Prepotentials Bradycardia Normal rhythm - 24 - Tachycardia 147029604 III. Smooth muscle Small, spindle-shaped cells arranged in sheets of opposing fibers. Generally two sheets with fibers at right angles to each other longitudinal and circular layers. The alternating contraction of layers results in peristalsis. Smooth muscle lacks highly structured neuromuscular junctions and has lower myosin to actin ratio than skeletal (1:13 vs. 1:2). It lacks troponin complex and sarcomeres. Electrical communication between individual smooth muscle cells (gap junctions) make the entire sheet responds to a single stimulus. Some tissue has pacemaker cells and some are self-excitatory. The difference between smooth and skeletal is that Ca2+ interacts with regulatory molecules called calmodulin not troponin. Contraction is slow, sustained and resistant to fatigue. Smooth muscle has a unique property of depolarization and, hence, contraction in response to stretch. Smooth muscle also has the property of stress-relaxation (plasticity) which means that with gradual increase in stretch; tension firstly increase and then decrease even below its initial level. This property is of benefit especially in uterus in order to adapt to the continuous increase in fetal size and in urinary bladder to adapt to the continuous increase in urine volume. Smooth muscles are in continuous state of partial contraction (tone). Different types of nerve supply with multiple neurotransmitters are found in smooth muscles but their role is only to modify that muscle tone. Smooth muscle is also affected by other factors like chemicals, pH, temperature, CO 2, O2 ....etc Two types of smooth muscle are present: Single-unit smooth muscle: Function as syncytium. Found mainly in the wall of hollow viscera. - 25 - 147029604 Multi-unit smooth muscle: Has no gap junctions and each muscle works individually. Found in the iris of eye, vas deferens, epididymus, large pulmonary airways and large blood vessels. They have many functional similarities to skeletal muscles but irregularly and involuntarily contract with prolonged duration. - 26 - 147029604 Comparison of skeletal, cardiac and smooth Muscle Characteristic Location Appearance Connective Tissue Sarcomere T Tubules Gap Junctions Neuromuscular Junctions Regulation of Contraction Skeletal Attached to bones, fascia and skin Single, long, cylindrical, striated, multinucleate Epimysium, perimysium, endomysium Present Present at each end None Present Cardiac Walls of heart Present Present at one end Intercalated discs None None None Somatic NS; voluntary Autonomic NS, intrinsic (pacemaker), hormones, involuntary SR, extracellular fluid Via troponin/actin interactions Present Excitation or inhibition Slow Autonomic NS, hormones, local regulation, response to stretch Yes In single-unit Strength of contraction increases Aerobic Stress-relaxation response (plasticity) Ca2+ Source SR Role of Ca2+ Via troponin/actin interactions None Excitation Pacemakers Nervous System Affects Speed of Contraction Rhythmic Contraction Response to Stretch Respiration Varies: slow to fast None Strength of contraction increases Aerobic or anaerobic Smooth Single-unit: visceral organs Multi-unit: Internal eye muscles, large airways and arteries Branching chains Single, non-striated, uninucleate of cells, uninucleate, striated Endomysium Endomysium - 27 - In single-unit In multiunit SR, extracellular fluid Via calmodulin/myosin interaction In single-unit Excitation or inhibition Very slow Primarily anaerobic