Muscles Physiology PDF

Muscles Physiology Muscular System Functions ▪ Body movement (Locomotion) ▪ Maintenance of posture ▪ Respiration ▪ Diaphragm and intercostal contractions ▪ Communication (Verbal and Facial) ▪ Constriction of organs and vessels ▪ Peristalsis of intestinal tract ▪ Vasoconstriction of b.v. a...

Muscles Physiology Muscular System Functions ▪ Body movement (Locomotion) ▪ Maintenance of posture ▪ Respiration ▪ Diaphragm and intercostal contractions ▪ Communication (Verbal and Facial) ▪ Constriction of organs and vessels ▪ Peristalsis of intestinal tract ▪ Vasoconstriction of b.v. and other structures (pupils) ▪ Heart beat ▪ Production of body heat (Thermogenesis) Properties of Muscle ▪ Excitability: capacity of muscle to respond to a stimulus ▪ Contractility: ability of a muscle to shorten and generate pulling force ▪ Extensibility: muscle can be stretched back to its original length ▪ Elasticity: ability of muscle to recoil to original resting length after stretched Types of Muscle ▪ Skeletal ▪ Attached to bones ▪ Makes up 40% of body weight ▪ Responsible for locomotion, facial expressions, posture, respiratory movements, other types of body movement ▪ Voluntary in action; controlled by somatic motor neurons ▪ Smooth ▪ In the walls of hollow organs, blood vessels, eye, glands, uterus, skin ▪ Some functions: propel urine, mix food in digestive tract, dilating/constricting pupils, regulating blood flow, ▪ In some locations, autorhythmic ▪ Controlled involuntarily by endocrine and autonomic nervous systems ▪ Cardiac ▪ Heart: major source of movement of blood ▪ Autorhythmic ▪ Controlled involuntarily by endocrine and autonomic nervous systems Connective Tissue Sheaths ▪ Connective Tissue of a Muscle ▪ Epimysium. Dense regular c.t. surrounding entire muscle ▪ Separates muscle from surrounding tissues and organs ▪ Connected to the deep fascia ▪ Perimysium. Collagen and elastic fibers surrounding a group of muscle fibers called a fascicle ▪ Contains b.v and nerves ▪ Endomysium. Loose connective tissue that surrounds individual muscle fibers ▪ Also contains b.v., nerves, and satellite cells (embryonic stem cells function in repair of muscle tissue ▪ Collagen fibers of all 3 layers come together at each end of muscle to form a tendon or aponeurosis. Nerve and Blood Vessel Supply ▪ Motor neurons ▪ stimulate muscle fibers to contract ▪ Neuron axons branch so that each muscle fiber (muscle cell) is innervated ▪ Form a neuromuscular junction (= myoneural junction) ▪ Capillary beds surround muscle fibers ▪ Muscles require large amts of energy ▪ Extensive vascular network delivers necessary oxygen and nutrients and carries away metabolic waste produced by muscle fibers Muscle Tissue Types Skeletal Muscle ▪ Long cylindrical cells ▪ Many nuclei per cell ▪ Striated ▪ Voluntary ▪ Rapid contractions Basic Features of a Skeletal Muscle ▪ Muscle attachments ▪ Most skeletal muscles run from one bone to another ▪ One bone will move – other bone remains fixed ▪ Origin – less movable attach- ment ▪ Insertion – more movable attach- ment Basic Features of a Skeletal Muscle ▪ Muscle attachments (continued) ▪ Muscles attach to origins and insertions by connective tissue ▪ Fleshy attachments – connective tissue fibers are short ▪ Indirect attachments – connective tissue forms a tendon or aponeurosis ▪ Bone markings present where tendons meet bones ▪ Tubercles, trochanters, and crests Skeletal Muscle Structure ▪ Composed of muscle cells (fibers), connective tissue, blood vessels, nerves ▪ Fibers are long, cylindrical, and multinucleated ▪ Tend to be smaller diameter in small muscles and larger in large muscles. 1 mm- 4 cm in length ▪ Develop from myoblasts; numbers remain constant ▪ Striated appearance ▪ Nuclei are peripherally located Muscle Attachments Antagonistic Muscles Microanatomy of Skeletal Muscle Muscle Fiber Anatomy ▪ Sarcolemma - cell membrane ▪ Surrounds the sarcoplasm (cytoplasm of fiber) ▪ Contains many of the same organelles seen in other cells ▪ An abundance of the oxygen-binding protein myoglobin ▪ Punctuated by openings called the transverse tubules (T- tubules) ▪ Narrow tubes that extend into the sarcoplasm at right angles to the surface ▪ Filled with extracellular fluid ▪ Myofibrils -cylindrical structures within muscle fiber ▪ Are bundles of protein filaments (=myofilaments) ▪ Two types of myofilaments 1.Actin filaments (thin filaments) 2.Myosin filaments (thick filaments) – At each end of the fiber, myofibrils are anchored to the inner surface of the sarcolemma – When myofibril shortens, muscle shortens (contracts) Sarcoplasmic Reticulum (SR) ▪ SR is an elaborate, smooth endoplasmic reticulum ▪ runs longitudinally and surrounds each myofibril ▪ Form chambers called terminal cisternae on either side of the T-tubules ▪ A single T-tubule and the 2 terminal cisternae form a triad ▪ SR stores Ca++ when muscle not contracting ▪ When stimulated, calcium released into sarcoplasm ▪ SR membrane has Ca++ pumps that function to pump Ca++ out of the sarcoplasm back into the SR after contraction Sarcoplasmic Reticulum (SR) Parts of a Muscle Sarcomeres: Z Disk to Z Disk ▪ Sarcomere - repeating functional units of a myofibril ▪ About 10,000 sarcomeres per myofibril, end to end ▪ Each is about 2 µm long ▪ Differences in size, density, and distribution of thick and thin filaments gives the muscle fiber a banded or striated appearance. ▪ A bands: a dark band; full length of thick (myosin) filament ▪ M line - protein to which myosins attach ▪ H zone - thick but NO thin filaments ▪ I bands: a light band; from Z disks to ends of thick filaments ▪ Thin but NO thick filaments ▪ Extends from A band of one sarcomere to A band of the next sarcomere ▪ Z disk: filamentous network of protein. Serves as attachment for actin myofilaments ▪ Titin filaments: elastic chains of amino acids; keep thick and thin filaments in proper alignment Structure of Actin and Myosin Myosin (Thick) ▪ Many elongated myosin molecules shaped like golf clubs. Myofilament ▪ Single filament contains roughly 300 myosin molecules ▪ Molecule consists of two heavy myosin molecules wound together to form a rod portion lying parallel to the myosin myofilament and two heads that extend laterally. ▪ Myosin heads 1. Can bind to active sites on the actin molecules to form cross-bridges. (Actin binding site) 2. Attached to the rod portion by a hinge region that can bend and straighten during contraction. 3. Have ATPase activity: activity that breaks down adenosine triphosphate (ATP), releasing energy. Part of the energy is used to bend the hinge region of the myosin molecule during contraction ▪ Thin Filament: composed of 3 major proteins Actin (Thin) 1. F (fibrous) actin 2. Tropomyosin Myofilaments 3. Troponin ▪ Two strands of fibrous (F) actin form a double helix extending the length of the myofilament; attached at either end at sarcomere. ▪ Composed of G actin monomers each of which has a myosin-binding site (see yellow dot) ▪ Actin site can bind myosin during muscle contraction. ▪ Tropomyosin: an elongated protein winds along the groove of the F actin double helix. ▪ Troponin is composed of three subunits: ▪ Tn-A : binds to actin ▪ Tn-T :binds to tropomyosin, ▪ Tn-C :binds to calcium ions. Contraction of Skeletal Muscle Fibers ▪ Contraction – refers to the activation of myosin’s cross bridges (force-generating sites) ▪ Shortening occurs when the tension generated by the cross bridge exceeds forces opposing shortening ▪ Contraction ends when cross bridges become inactive, the tension generated declines, and relaxation is induced Contraction of Skeletal Muscle (Organ Level) ▪ Contraction of muscle fibers (cells) and muscles (organs) is similar ▪ The two types of muscle contractions are: ▪ Isometric contraction – increasing muscle tension (muscle does not shorten during contraction) ▪ Isotonic contraction – decreasing muscle length (muscle shortens during contraction)  Biceps muscle shortens during contraction shortening (Isotonic: shortening against fixed load, speed dependent on M·ATPase activity and load) isometric Most likely to cause lengthening Biceps muscle lengthens muscle injury during contraction Sliding Filament Model of Contraction ▪ Thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree ▪ In the relaxed state, thin and thick filaments overlap only slightly ▪ Upon stimulation, myosin heads bind to actin and sliding begins The Sliding Filament Model The lever movement drives displacement of the actin filament relative to the myosin head (~5 nm), and by deforming internal elastic structures, produces force (~5 pN). Thick and thin filaments interdigitate and “slide” relative to each other. Contraction Z line Z line Myosin is a Molecular Motor Myosin is a hexamer: 2 myosin heavy chains 4 myosin light chains Coiled coil of two a helices 2 nm C terminus Myosin head: retains all of the motor functions of myosin, i.e. the ability to produce movement and force. Nucleotide binding site Myosin S1 fragment crystal structure NH2-terminal catalytic neck region/lever arm Ruegg et al., (2002) (motor) domain News Physiol Sci 17:213-218. H Band Sarcomere Relaxed Sarcomere Partially Contracted Sarcomere Completely Contracted Skeletal Muscle Contraction ▪ In order to contract, a skeletal muscle must: ▪ Be stimulated by a nerve ending ▪ Propagate an electrical current, or action potential, along its sarcolemma ▪ Have a rise in intracellular Ca2+ levels, the final trigger for contraction ▪ Linking the electrical signal to the contraction is excitation-contraction coupling Role of Ionic Calcium (Ca2+) in the Contraction Mechanism ▪ At low intracellular Ca2+ concentration: ▪ Tropomyosin blocks the binding sites on actin ▪ Myosin cross bridges cannot attach to binding sites on actin ▪ The relaxed state of the muscle is enforced Figure 9.10 (a) Role of Ionic Calcium (Ca2+) in the Contraction Mechanism ▪ At higher intracellular Ca2+ concentrations: ▪ Additional calcium binds to troponin (inactive troponin binds two Ca2+) ▪ Calcium-activated troponin binds an additional two Ca2+ at a separate regulatory site Figure 9.10 (b) Role of Ionic Calcium (Ca2+) in the Contraction Mechanism ▪ Calcium-activated troponin undergoes a conformational change ▪ This change moves tropomyosin away from actin’s binding sites Figure 9.10 (c) Role of Ionic Calcium (Ca2+) in the Contraction Mechanism ▪ Myosin head can now bind and cycle ▪ This permits contraction (sliding of the thin filaments by the myosin cross bridges) to begin Figure 9.10 (d) Sequential Events of Contraction ▪ Cross bridge formation – myosin cross bridge attaches to actin filament ▪ Working (power) stroke – myosin head pivots and pulls actin filament toward M line ▪ Cross bridge detachment – ATP attaches to myosin head and the cross bridge detaches ▪ “Cocking” of the myosin head – energy from hydrolysis of ATP cocks the myosin head into the high-energy state Sequential Events of Contraction Myosin head (high-energy configuration) 1 Myosin cross bridge attaches to the actin myofilament Thin filament Thick ADP and Pi (inorganic filament phosphate) released 4 As ATP is split into ADP and Pi, 2 Working stroke—the myosin head pivots and cocking of the myosin head occurs bends as it pulls on the actin filament, sliding it toward the M line Myosin head (low-energy configuration) 3 As new ATP attaches to the myosin head, the cross bridge detaches Figure 9.11 Binding Site Tropomyosin Ca2+ Troponin Myosin Neuromuscular Junction ▪ When a nerve impulse reaches the end of an axon at the neuromuscular junction: ▪ Voltage-regulated calcium channels open and allow Ca2+ to enter the axon ▪ Ca2+ inside the axon terminal causes axonal vesicles to fuse with the axonal membrane Neuromuscular Junction ▪ This fusion releases ACh into the synaptic cleft via exocytosis ▪ ACh diffuses across the synaptic cleft to ACh receptors on the sarcolemma ▪ Binding of ACh to its receptors initiates an action potential in the muscle Destruction of Acetylcholine ▪ ACh bound to ACh receptors is quickly destroyed by the enzyme acetylcholinesterase ▪ This destruction prevents continued muscle fiber contraction in the absence of additional stimuli Action Potential ▪ A transient depolarization event that includes polarity reversal of a sarcolemma (or nerve cell membrane) and the propagation of an action potential along the membrane Role of Acetylcholine (Ach) ▪ ACh binds its receptors at the motor end plate ▪ Binding opens chemically (ligand) gated channels ▪ Na+ and K+ diffuse out and the interior of the sarcolemma becomes less negative ▪ This event is called depolarization Depolarization ▪ Initially, this is a local electrical event called end plate potential ▪ Later, it ignites an action potential that spreads in all directions across the sarcolemma Action Potential: Electrical Conditions of a Polarized Sarcolemma ▪ The outside (extracellular) face is positive, while the inside face is negative ▪ This difference in charge is the resting membrane potential Figure 9.8 (a) Action Potential: Electrical Conditions of a Polarized Sarcolemma ▪ The predominant extracellular ion is Na+ ▪ The predominant intracellular ion is K+ ▪ The sarcolemma is relatively impermeable to both ions Figure 9.8 (a) Action Potential: Depolarization and Generation of the Action Potential ▪ An axonal terminal of a motor neuron releases ACh and causes a patch of the sarcolemma to become permeable to Na+ (sodium channels open) Figure 9.8 (b) Action Potential: Depolarization and Generation of the Action Potential ▪ Na+ enters the cell, and the resting potential is decreased (depolarization occurs) ▪ If the stimulus is strong enough, an action potential is initiated Figure 9.8 (b) Action Potential: Propagation of the Action Potential ▪ Polarity reversal of the initial patch of sarcolemma changes the permeability of the adjacent patch ▪ Voltage-regulated Na+ channels now open in the adjacent patch causing it to depolarize Figure 9.8 (c) Action Potential: Propagation of the Action Potential ▪ Thus, the action potential travels rapidly along the sarcolemma ▪ Once initiated, the action potential is unstoppable, and ultimately results in the contraction of a muscle Figure 9.8 (c) Action Potential: Repolarization ▪ Immediately after the depolarization wave passes, the sarcolemma permeability changes ▪ Na+ channels close and K+ channels open ▪ K+ diffuses from the cell, restoring the electrical polarity of the sarcolemma Figure 9.8 (d) Action Potential: Repolarization ▪ Repolarization occurs in the same direction as depolarization, and must occur before the muscle can be stimulated again (refractory period) ▪ The ionic concentration of the resting state is restored by the Na+-K+ pump Figure 9.8 (d) Excitation-Contraction Coupling Muscle contraction ▪ Alpha motor neurons release Ach ▪ ACh produces large EPSP in muscle fibers (via nicotinic Ach receptors ▪ EPSP evokes action potential ▪ Action potential (excitation) triggers Ca2+ release, leads to fiber contraction ▪ Relaxation, Ca2+ levels lowered by organelle reuptake Excitation-Contraction Coupling ▪ Once generated, the action potential: ▪ Is propagated along the sarcolemma ▪ Travels down the T tubules ▪ Triggers Ca2+ release from terminal cisternae ▪ Ca2+ binds to troponin and causes: ▪ The blocking action of tropomyosin to cease ▪ Actin active binding sites to be exposed Excitation-Contraction Coupling ▪ Myosin cross bridges alternately attach and detach ▪ Thin filaments move toward the center of the sarcomere ▪ Hydrolysis of ATP powers this cycling process ▪ Ca2+ is removed into the SR, tropomyosin blockage is restored, and the muscle fiber relaxes Excitation-Contraction Coupling Excitation-Contraction Coupling Neuromuscular Junction Neuromuscular Junction ▪ Region where the motor neuron stimulates the muscle fiber ▪ The neuromuscular junction is formed by : 1. End of motor neuron axon (axon terminal) ▪ Terminals have small membranous sacs (synaptic vesicles) that contain the neurotransmitter acetylcholine (ACh) 2. The motor end plate of a muscle A specific part of the sarcolemma that contains ACh receptors ▪ Though exceedingly close, axonal ends and muscle fibers are always separated by a space called the synaptic cleft Neuromuscular Junction Acetylcholine Opens Na+ Channel Muscle Fiber Types (continued) ▪ Smaller slow twitch motor units are characterized as tonic units, red in appearance, smaller muscle fibers, fibers rich in mitochondria, highly capillarized, high capacity for aerobic metabolism, and produce low peak tension in a long time to peak (60-120ms). ▪ Larger fast twitch motor units are characterized as phasic units, white in appearance, larger muscle fibers, less mitochondria, poorly capillarized, rely on anaerobic metabolism, and produce large peak tensions in shorter periods of time (10-50ms). Muscle Fiber Types (continued) ▪ Nerve innervating muscle fiber determines its type; possible to change fiber type by changing innervations of fiber ▪ All fibers of motor unit are of same type ▪ Fiber type distribution in muscle genetically determined ▪ Average population distribution: ▪ 50-55% type I ▪ 30-35% type IIA ▪ 15% type IIB Muscle Fiber Types (continued) ▪ Fiber composition of muscle relates to function (e.g., soleus – posture muscle, high percentage type I) ▪ Muscles mixed in fiber type composition ▪ Natural selection of athletes at top levels of competition  Muscle Fiber Types Type I Type IIA Type IIB Slow-Twitch Fast-Twitch Fast-Twitch Oxidative (SO) Oxidative- Glycolytic (FG) Glycolytic (FOG) Speed of Slow Fast Fast contraction Primary source of Oxidative Oxidative Anaerobic ATP production phosphorylation phosphorylation glycolysis Glycolytic enzyme Low Intermediate High activity Capillaries Many Many Few Myoglobin content High High Low Glycogen content Low Intermediate High Fiber diameter Small Intermediate Large Rate of fatigue Slow Intermediate Fast Motor Unit: The Nerve-Muscle Functional Unit ▪ A motor unit is a motor neuron and all the muscle fibers it supplies ▪ The number of muscle fibers per motor unit can vary from a few (4-6) to hundreds (1200-1500) ▪ Muscles that control fine movements (fingers, eyes) have small motor units ▪ Large weight-bearing muscles (thighs, hips) have large motor units Motor Unit: The Nerve-Muscle Functional Unit ▪ Muscle fibers from a motor unit are spread throughout the muscle ▪ Not confined to one fascicle ▪ Therefore, contraction of a single motor unit causes weak contraction of the entire muscle ▪ Stronger and stronger contractions of a muscle require more and more motor units being stimulated (recruited) Motor Unit All the muscle cells controlled by one nerve cell Muscle Contraction Summary ▪ Nerve impulse reaches myoneural junction ▪ Acetylcholine is released from motor neuron ▪ Ach binds with receptors in the muscle membrane to allow sodium to enter ▪ Sodium influx will generate an action potential in the sarcolemma Muscle Contraction summary (Cont’d) ▪ Action potential travels down T tubule ▪ Sarcoplamic reticulum releases calcium ▪ Calcium binds with troponin to move the troponin, tropomyosin complex ▪ Binding sites in the actin filament are exposed Muscle Contraction summary (cont’d) ▪ Myosin head attach to binding sites and create a power stroke ▪ ATP detaches myosin heads and energizes them for another contaction ▪ When action potentials cease the muscle stop contracting Contraction Speed Chemomechanical coupling – conversion of chemical energy (ATP about 7 kcal x mole-1) into force/movement. ATP is unstable thermodynamically Two most energetically favorable steps: 1. ATP binding to myosin 2. Phosphate release from myosin Rate of cycling determined by M·ATPase activity and external load Adapted from Goldman & Brenner (1987) Ann Rev Physiol 49:629-636. Motor Unit: The Nerve-Muscle Functional Unit ▪ A motor unit is a motor neuron and all the muscle fibers it supplies ▪ The number of muscle fibers per motor unit can vary from four to several hundred ▪ Muscles that control fine movements (fingers, eyes) have small motor units Motor Unit: The Nerve-Muscle Functional Unit Figure 9.12 (a) Motor Unit: The Nerve-Muscle Functional Unit ▪ Large weight-bearing muscles (thighs, hips) have large motor units ▪ Muscle fibers from a motor unit are spread throughout the muscle; therefore, contraction of a single motor unit causes weak contraction of the entire muscle Muscle Spindles ▪ Are composed of 3-10 intrafusal muscle fibers that lack myofilaments in their central regions, are noncontractile, and serve as receptive surfaces ▪ Muscle spindles are wrapped with two types of afferent endings: primary sensory endings of type Ia fibers and secondary sensory endings of type II fibers ▪ These regions are innervated by gamma () efferent fibers ▪ Note: contractile muscle fibers are extrafusal fibers and are innervated by alpha (a) efferent fibers Muscle Spindles Figure 13.15 Operation of the Muscle Spindles ▪ Stretching the muscles activates the muscle spindle ▪ There is an increased rate of action potential in Ia fibers ▪ Contracting the muscle reduces tension on the muscle spindle ▪ There is a decreased rate of action potential on Ia fibers Operation of the Muscle Spindles Figure 13.16 Muscle Twitch ▪ A muscle twitch is the response of a muscle to a single, brief threshold stimulus ▪ The three phases of a muscle twitch are: ▪ Latent period – first few milli- seconds after stimulation when excitation- contraction coupling is taking place Figure 9.13 (a) Muscle Twitch ▪ Period of contraction – cross bridges actively form and the muscle shortens ▪ Period of relaxation – Ca2+ is reabsorbed into the SR, and muscle tension goes to zero Figure 9.13 (a) Graded Muscle Responses ▪ Graded muscle responses are: ▪ Variations in the degree of muscle contraction ▪ Required for proper control of skeletal movement ▪ Responses are graded by: ▪ Changing the frequency of stimulation ▪ Changing the strength of the stimulus Muscle Response to Varying Stimuli ▪ A single stimulus results in a single contractile response – a muscle twitch ▪ Frequently delivered stimuli (muscle does not have time to completely relax) increases contractile force – wave summation Figure 9.14 Muscle Response to Varying Stimuli ▪ More rapidly delivered stimuli result in incomplete tetanus ▪ If stimuli are given quickly enough, complete tetanus results Figure 9.14 Tetanus Muscle Response: Stimulation Strength ▪ Threshold stimulus – the stimulus strength at which the first observable muscle contraction occurs ▪ Beyond threshold, muscle contracts more vigorously as stimulus strength is increased ▪ Force of contraction is precisely controlled by multiple motor unit summation ▪ This phenomenon, called recruitment, brings more and more muscle fibers into play Stimulus Intensity and Muscle Tension Figure 9.15 (a, b) Treppe: The Staircase Effect ▪ Staircase – increased contraction in response to multiple stimuli of the same strength ▪ Contractions increase because: ▪ There is increasing availability of Ca2+ in the sarcoplasm ▪ Muscle enzyme systems become more efficient because heat is increased as muscle contracts Treppe: The Staircase Effect Figure 9.16 Smooth Muscle ▪ Fusiform cells ▪ One nucleus per cell ▪ Nonstriated ▪ Involuntary ▪ Slow, wave-like contractions Smooth Muscle ▪ Cells are not striated ▪ Fibers smaller than those in skeletal muscle ▪ Spindle-shaped; single, central nucleus ▪ More actin than myosin ▪ No sarcomeres ▪ Not arranged as symmetrically as in skeletal muscle, thus NO striations. ▪ Caveolae: indentations in sarcolemma; ▪ May act like T tubules ▪ Dense bodies instead of Z disks ▪ Have noncontractile intermediate filaments Smooth Muscle Grouped into sheets in walls of hollow organs Longitudinal layer – muscle fibers run parallel to organ’s long axis Circular layer – muscle fibers run around circumference of the organ Both layers participate in peristalsis Smooth Muscle ▪ Is innervated by autonomic nervous system (ANS) ▪ Visceral or unitary smooth muscle ▪ Only a few muscle fibers innervated in each group ▪ Impulse spreads through gap junctions ▪ Who sheet contracts as a unit ▪ Often autorhythmic ▪ Multiunit: ▪ Cells or groups of cells act as independent units ▪ Arrector pili of skin and iris of eye Smooth muscle cell contraction ▪ Smooth muscle contraction is not controlled by the binding of Ca+2 to the troponin complex ▪ Ca+2 control myosin attachment to the actin through an intermediate step of Ca+2/calmodulin and it is this that controls contraction in smooth muscle cells. ▪ Troponin is not found in smooth muscle cells (tropomyosin is). Smooth Muscle Cell Smooth Muscle Cell Organization of cytoskeletal and myofilaments Smooth Muscle Contraction: Mechanism Smooth Muscle Relaxation: Mechanism Smooth muscle contraction Regulation of smooth muscle contraction ▪ Controlled through changes in resting membrane potential. ▪ Depolarization causes a greater increase in cytosolic Ca+2 and thus greater contraction. ▪ Hyperpolarization causes a reduced amount of cytosolic Ca+2 and thus relaxes the muscle cell. ▪ Release of Ca+2 from internal stores may also lead to greater contraction through G protein mediated cascades that have nothing to do with changes in membrane depolarization. Single-Unit Muscle Properties of Single-Unit Smooth Muscle ▪ Gap junctions ▪ Graded Contractions ▪ Pacemaker cells ▪ No recruitment with spontaneous ▪ Vary intracellular depolarizations calcium ▪ Innervation to few cells ▪ Stretch Reflex ▪ Tone = level of ▪ Relaxation in contraction without response to sudden stimulation or prolonged stretch ▪ Increases/decreases in tension Multi-Unit Muscle Multi vs. Single-Unit Muscle Comparisons Among Skeletal, Smooth, and Cardiac Muscle