Muscular SystemPart B

Muscular mechanics

• 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.

• Give a series of identical stimuli - series of twitch contractions with complete relaxation in between contractions

• Strength of contractions increases slightly each time – staircase effect or treppe

Time

• Latent period – Ca++ is released, filament movement takes up slack – 2 milliseconds

• Contraction period – 10 – 100 milliseconds

• Relaxation period - 10 – 100 milliseconds

• Refractory period – time after a contraction until the muscle is able to respond to a second stimulus.– Skeletal muscle – 5 msec– Cardiac muscle – 300 msec (0.3 sec)

• 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.

Sustained contraction

Tetanic contraction

Muscle fiber length

Whole muscle myogram• A brief, single stimulus results in a twitch

contraction.

• A twitch is a brief contraction of all the muscle fibers in a motor unit.

• 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.

• 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 .

Types of muscle contraction

• Isotonic contraction (iso = same, tonus = tension) results in movement at a joint– Because shortening of the muscle occurs it is called

a concentric contraction.– When the muscle lengthens it is called an eccentric

contraction.

• Isometric contraction (iso= same, metric = measure) the force of contraction changes, but the muscle length remains the same.

Cardiac Muscle – similar to skeletal muscle in:

• Striations – caused by organization of myofilaments

• Contains troponin and tropomyosin – site of activation of cross-bridge activity by Ca++

• Clear length-tension relationship

• Numerous mitochondria and myoglobin (for aerobic respiration)

• T tubules and moderately well developed sarcoplasmic reticulum (T tubule at Z line)

Cardiac Muscle – differs from skeletal muscle in:

• Shorter, larger diameter than skeletal muscle

• Branch, forming 3-D networks

• Usually only one nucleus

• Autorythmicity –influenced by nervous system and hormones

• Sarcoplasm is more abundant with more mitochondria

• Only one t-tubule per sarcomere

• 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 junctions

• Two networks – atria and ventricles – cells contract together linked by gap junctions - functional syncytium

Cardiac muscle physiology

• Contraction starts at the pacemaker or sinoatrial node.

• Autorhythmicity

• Contraction due in large part to influx of Ca++ from ECF

• Resting potential of -90 mV

• Opening of voltage-gated Na+ channels reverses polarity to +30 mV

• 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 10-15 times longer

• Long refractory period– Allows for filling of heart chambers– Prevents tetanic contractions

• 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 contractility

• In 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)

• DHP channels: RyR is 1:1

• Release of “calcium sparks” sum to trigger release

• Increased cytosolic calcium

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 sarcolemma

• Na+/Ca++ exchange proteins (3:1 ; secondary active transport)

Effects of extracellular K+ on heart

• Changes in K+ in ECF alter the concentration gradient across sarcolemma– Leads to ectopic foci and cardiac arrhythmias– Decrease in action potential leads to weak

contractions and dilation of heart– At extremes, heart can stop

Effects of extracellular Ca++ on heart

• Rise in ECF Ca++ increases strength of contraction by prolonging plateau phase– Tends to contract spastically– Drugs can influence Ca++ movement across

sarcolemma (calcium channel blockers, digitalis e.g.)

Inotropy• Positive inotropes increase contractility of heart

– Sympathetic nervous system stimulation– Catecholamine hormones (epinephrine)– Digitalis – Increased heart rate

• Negative inotropes decrease contractility– Decreased heart rate– Coronary artery disease– Certain drugs (calcium channel blockers)

Starling’s Law

• Within 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

Smooth muscle• Nonstriated and involuntary

• Cells smaller than skeletal muscle cells

• Spindle-shaped

• Single nucleus

• NO T tubules

• Different arrangement of myofilaments

• Thin, thick and intermediate filaments

Smooth muscle• Thick and thin filaments not arranged in

sarcomeres

• Thick filaments are longer than in skeletal muscle

• Thin filaments lack troponin

• 10-15 thin filaments/ thick (skeletal 2:1)

• Intermediate fibers act as cytoskeleton

• Typically less SR than in skeletal muscle

• Intermediate filaments attach to dense bodies ( act like Z discs)

• Intermediate fibers connect dense bodies

• Thick- and thin-filament contractile units oriented slightly diagonally in a diamond-shaped lattice pattern

• Contraction causes the lattice to decrease in length and expand from side to side.

• 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.

Gap Junctions• Often connect smooth muscle cells

• May be temporary, and may be under hormonal control

• The electrical joining of smooth muscle cells is the basis for classifying smooth muscle into two types:Visceral (single-unit) smooth muscle

• Many cells acting together

Multiunit smooth muscle• Cells contract in small groups

Single-unit smooth muscle

Multiunit Smooth Muscle

Visceral (single-unit) smooth muscle

• More common type

• Wrap-around sheets

• Fibers form networks that contract together

• Connected by gap junctions

• Some cells also have autorhythmicity

• Largely responsible for peristalsis

Multiunit Smooth Muscle

• Individual fibers within motor units; few gap junctions

• In walls of large arteries, large airways, arrector pili, iris muscles and ciliary body in eye.

• Contracts only after stimulation by motor neuron or hormones

Physiology of Smooth Muscle

• Contractions start slower and last longer

• Can shorten and extend to greater extent

• Resting 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”

• Sodium is not the major carrier of current during an action potential, instead it is Ca2+ which enters through voltage-gated channels

• Also have receptor-activated or chemically activated Ca2+ channels

• Repolarization due to outflow of K+ though voltage-gated channels and some channels sensitive to intracellular Ca2+ levels

Physiology of Smooth Muscle• Calcium ions come from the small amount

of S.R. and from extracellular fluid through DHP channels

• Instead of troponin, contains calmodulin which regulates contraction

• Myosin-linked regulation

• Camodulin binds with Ca++ and activates myosin light chain kinase (MLCK)

• MLCK uses ATP to add a phosphate group to the myosin head. Myosin can then bind to actin

• ATP for actual contraction is separate

• Enzymes work slowly (100 x slower than skeletal muscle)

• Calmodulin is sensitive to Ca2+ conc. in ICF– At 10-7 M Ca2+ , no calcium is bound– At 10-4 M Ca2+ all 4 calmodulin sites are bound and

rate of phosphorylation is maximal– In between see gradations in contractile force

Relaxation of Smooth Muscle

• When Ca2+ levels fall, calmodulin is no longer active and phosphorylation of myosin is reversed by the enzyme myosin light-chain phosphotase (MLCP)

• 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

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 receptors

• Many 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+

Origin and Insertions

• Origin – the attachment of a muscle to the less movable part (torso, etc.)

• Insertion – the attachment of a muscle to the more movable part

Interactions of muscles

• Prime mover – the muscle primarily responsible for a movement

• Synergist – stabilizes or assists prime mover

• Antagonist – opposes action of prime mover and must relax for prime mover to contract completely

Major muscles will be covered in lab.

Life Span Changes• Develops from mesoderm cells called

myoblasts

• Multinucleate skeletal muscle cells form through fusion of myoblasts to form myotubes

• Fibers are contracting at 7 weeks

• ACh receptors sprout over surface of myoblast

• Agrin released by nerve endings stimulates clustering of ACh receptors

• Remaining receptor sites dispersed

• Electrical activity in the motor neurons plays a critical role in maturation of muscle fibers

• The 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.

Repair of muscle• Skeletal 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 middle

• Satellite cells (stem cells)repair injured fibers and may allow a very limited regeneration of fibers.

• Most repair by fibrosis

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

Repair of Smooth Muscle• Limited to good capacity for division and

regeneration throughout life

• Some increase due to hyperplasia

• New fibers can arise from pericytes (stem cells)

• Proliferate in atheroscerolsis

Development • At birth movements are uncoordinated and

reflexive

• Develops head-to-toe and proximal-to-distal

• Through childhood control becomes more sophisticated.

• Early hand dominance

• Midadolescence reach peak of natural neural control of muscles

Male vs. Female

• Strength has a biological basis

• Women 36% muscle

• Men 42% muscle

• Primarily due to effects of testosterone

• Strength per unit mass is the same in both sexes

Aging changes• Connective 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.

• 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

• Impairment of synthesis of new muscle proteins

• Reduction in nerve activity due to changes in nervous system– Loss of motor neurons– Reduction in synthesis of ACh– Contributes to muscle fiber atrophy and

efficiency of stimulation