3 The minimal or smallest amount of stimulation that causes the muscle to contract is called the threshold stimulus.When a muscle cell receives a threshold stimulus, it contracts to its full extent – an all-or-none response.
8 Contraction period – 10 – 100 milliseconds Latent period – Ca++ is released, filament movement takes up slack – 2 millisecondsContraction period – 10 – 100 millisecondsRelaxation period - 10 – 100 millisecondsRefractory period – time after a contraction until the muscle is able to respond to a second stimulus.Skeletal muscle – 5 msecCardiac muscle – 300 msec (0.3 sec)
9 When stimuli do not allow muscle to relax completely between contractions, the muscle contraction becomes sustained.If stimulation is great enough, get a sustained contraction called a tetanic contraction or tetanus.
12 Whole muscle myogramA brief, single stimulus results in a twitch contraction.A twitch is a brief contraction of all the muscle fibers in a motor unit.
13 When a motor neuron fires, all of its muscle fibers contract fully. Some motor units are more easily stimulated than others.If only some of the motor units in a muscle contract, the entire muscle contracts partially.The process of adding more motor units for a greater muscle contraction is called recruitment or multiple motor unit summation.
14 To prevent fatigue, there is asynchronous recruitment of motor units. Recruitment varies with the type of muscle fibers.Muscles maintain a firmness at rest called muscle tone .
15 Types of muscle contraction Isotonic contraction (iso = same, tonus = tension) results in movement at a jointBecause shortening of the muscle occurs it is called a concentric contraction.When the muscle lengthens it is called an eccentric contraction.
19 Cardiac Muscle – similar to skeletal muscle in: Striations – caused by organization of myofilamentsContains troponin and tropomyosin – site of activation of cross-bridge activity by Ca++Clear length-tension relationshipNumerous mitochondria and myoglobin (for aerobic respiration)T tubules and moderately well developed sarcoplasmic reticulum (T tubule at Z line)
20 Cardiac Muscle – differs from skeletal muscle in: Shorter, larger diameter than skeletal muscleBranch, forming 3-D networksUsually only one nucleusAutorythmicity –influenced by nervous system and hormonesSarcoplasm is more abundant with more mitochondriaOnly one t-tubule per sarcomere
24 Well developed S.R., but less than skeletal muscle; cisternae store less Ca++. During contraction a lot of Ca++ enters cell from the extracellular fluid in the t-tubule and extracellular fluid around the cell, so extracellular calcium partially controls the strength and length of contraction.Intercalated discs – desmosomes; gap junctionsTwo networks – atria and ventricles – cells contract together linked by gap junctions - functional syncytium
26 Cardiac muscle physiology Contraction starts at the pacemaker or sinoatrial node.AutorhythmicityContraction due in large part to influx of Ca++ from ECFResting potential of -90 mVOpening of voltage-gated Na+ channels reverses polarity to +30 mV
27 Membrane potential rapidly reverses due to influx of Na+ Plateau phase lasts several hundred milliseconds due to slow influx of Ca++ (and slowing of exit of K+)Repolarization is due to rapid out flow of K+ ions.Remains contracted times longerLong refractory periodAllows for filling of heart chambersPrevents tetanic contractions
30 In skeletal muscle the amount of Ca2+ released is sufficient to bind all of the troponin molecules In cardiac muscle only a portion of troponin has bound Ca2+; allows for changes in contractilityIn cardiac muscle SR does not release enough Ca2+ to activate muscle contraction.Ca2+ entering cell during plateau phase triggers release of calcium from SR (calcium-induced calcium release)
31 DHP channels: RyR is 1:1Release of “calcium sparks” sum to trigger releaseIncreased cytosolic calcium
33 Removal of Ca2+ from cytosol Ca2+ATPase in SR runs continuously and is further activated by high cytoplasmic calcium levels (extracellular Ca++ that entered cell can be stored for next contraction)Also Ca2+ATPase located in sarcolemmaNa+/Ca++ exchange proteins (3:1 ; secondary active transport)
35 Effects of extracellular K+ on heart Changes in K+ in ECF alter the concentration gradient across sarcolemmaLeads to ectopic foci and cardiac arrhythmiasDecrease in action potential leads to weak contractions and dilation of heartAt extremes, heart can stop
36 Effects of extracellular Ca++ on heart Rise in ECF Ca++ increases strength of contraction by prolonging plateau phaseTends to contract spasticallyDrugs can influence Ca++ movement across sarcolemma (calcium channel blockers, digitalis e.g.)
38 Starling’s LawWithin certain physiological limits, an increase in the stretching of the ventricles causes an increase in the force of contraction of the heart.This allows for instantaneous regulation of contraction for increases in blood entering heart
39 Smooth muscle Nonstriated and involuntary Cells smaller than skeletal muscle cellsSpindle-shapedSingle nucleusNO T tubulesDifferent arrangement of myofilamentsThin, thick and intermediate filaments
41 Smooth muscle Thick and thin filaments not arranged in sarcomeres Thick filaments are longer than in skeletal muscleThin filaments lack troponin10-15 thin filaments/ thick (skeletal 2:1)Intermediate fibers act as cytoskeletonTypically less SR than in skeletal muscleIntermediate filaments attach to dense bodies ( act like Z discs)
42 Intermediate fibers connect dense bodies Thick- and thin-filament contractile units oriented slightly diagonally in a diamond-shaped lattice patternContraction causes the lattice to decrease in length and expand from side to side.
44 During contraction, the sliding thick and thin filaments generate tension that is transmitted to the intermediate filaments, which pull on the dense bodies in the sarcoplasm and those attached to the sarcolemma.Isolated smooth muscle cells contract by twisting into a helical shape, but this is prevented in intact tissues due to their attachment to other cells.
45 Gap Junctions Often connect smooth muscle cells May be temporary, and may be under hormonal controlThe electrical joining of smooth muscle cells is the basis for classifying smooth muscle into two types:Visceral (single-unit) smooth muscleMany cells acting togetherMultiunit smooth muscleCells contract in small groups
47 Visceral (single-unit) smooth muscle More common typeWrap-around sheetsFibers form networks that contract togetherConnected by gap junctionsSome cells also have autorhythmicityLargely responsible for peristalsis
48 Multiunit Smooth Muscle Individual fibers within motor units; few gap junctionsIn walls of large arteries, large airways, arrector pili, iris muscles and ciliary body in eye.Contracts only after stimulation by motor neuron or hormones
49 Physiology of Smooth Muscle Contractions start slower and last longerCan shorten and extend to greater extentResting potential is much lower and can vary over time due to automatic cyclical changes in the rate at which Na+ is pumped across the membrane.“Slow wave”
50 Sodium is not the major carrier of current during an action potential, instead it is Ca2+ which enters through voltage-gated channelsAlso have receptor-activated or chemically activated Ca2+ channelsRepolarization due to outflow of K+ though voltage-gated channels and some channels sensitive to intracellular Ca2+ levels
52 Physiology of Smooth Muscle Calcium ions come from the small amount of S.R. and from extracellular fluid through DHP channelsInstead of troponin, contains calmodulin which regulates contractionMyosin-linked regulationCamodulin binds with Ca++ and activates myosin light chain kinase (MLCK)
53 ATP for actual contraction is separate MLCK uses ATP to add a phosphate group to the myosin head. Myosin can then bind to actinATP for actual contraction is separateEnzymes work slowly (100 x slower than skeletal muscle)Calmodulin is sensitive to Ca2+ conc. in ICFAt 10-7 M Ca2+ , no calcium is boundAt 10-4 M Ca2+ all 4 calmodulin sites are bound and rate of phosphorylation is maximalIn between see gradations in contractile force
58 Ca2+ also leaves the cell slowly, which delays relaxation and provides for smooth muscle tone. Sustained tone is important, and in some cases smooth muscle can maintain a low level of active tension for long periods of time; a long sustained contraction is called tonus rather than tetanus
59 Regulation of Smooth Muscle contraction Responds to signals from autonomic nervous system ( responds to ACh and norepinephrine)Some have no nerve supply and depolarize spontaneously or to ligands that bind to G protein linked receptorsMany also contract or relax in response to stretching, hormones or local factors (such as changes in pH, oxygen or carbon dioxide levels, temperature or ion concentration).Enhances or inhibits entry of Ca2+
60 Origin and InsertionsOrigin – the attachment of a muscle to the less movable part (torso, etc.)Insertion – the attachment of a muscle to the more movable part
62 Interactions of muscles Prime mover – the muscle primarily responsible for a movementSynergist – stabilizes or assists prime moverAntagonist – opposes action of prime mover and must relax for prime mover to contract completely
64 Life Span Changes Develops from mesoderm cells called myoblasts Multinucleate skeletal muscle cells form through fusion of myoblasts to form myotubesFibers are contracting at 7 weeksACh receptors sprout over surface of myoblastAgrin released by nerve endings stimulates clustering of ACh receptors
65 Remaining receptor sites dispersed Electrical activity in the motor neurons plays a critical role in maturation of muscle fibersThe number of fast and slow fiber types is determined.Myoblasts producing cardiac and smooth muscle fibers do not fuse. Both develop gap junctions early. Cardiac muscle is pumping blood 3 weeks after fertilization.
66 Repair of muscleSkeletal and cardiac muscle cells stop dividing early, but retain ability to lengthen and thicken in a growing child and to hypertrophy in adults.After first year, growth of skeletal muscle is by hypertrophy.Enlarged fibers may split down middleSatellite cells (stem cells)repair injured fibers and may allow a very limited regeneration of fibers.Most repair by fibrosis
67 Repair of cardiac muscle Cardiac fibers do divide at a modest rate.Injured heart muscle repaired mostly by fibrosis (scar tissue).Fibers can hypertrophy and enlarge heart
68 Repair of Smooth Muscle Limited to good capacity for division and regeneration throughout lifeSome increase due to hyperplasiaNew fibers can arise from pericytes (stem cells)Proliferate in atheroscerolsis
69 Development At birth movements are uncoordinated and reflexive Develops head-to-toe and proximal-to-distalThrough childhood control becomes more sophisticated.Early hand dominanceMidadolescence reach peak of natural neural control of muscles
70 Male vs. Female Strength has a biological basis Women 36% muscle Primarily due to effects of testosteroneStrength per unit mass is the same in both sexes
71 Aging changesConnective tissue and fat increase and there is a slow, continuous reduction in the number of muscle fibers and loss of strength.At age 30 sarcopenia begins to occur as proteins degrade faster than they are replaced. (regulatory molecules?)Up to 30% of muscle fibers may be lost by age of 80.
72 Loss of fibers reduces size of motor units More motor units must be recruited to move a given weight, so requires more effort.Fast-twitch glycolytic fibers atrophy earlier than slow-twitch oxidative fibers.Posture not affected until very late in life.Reduction of ability of muscle to adapt to exercise.Some loss is disuse atrophy
73 Impairment of synthesis of new muscle proteins Reduction in nerve activity due to changes in nervous systemLoss of motor neuronsReduction in synthesis of AChContributes to muscle fiber atrophy and efficiency of stimulation