40% body weight

striated

multinucleated

voluntary movement

innervated by cerebrospinal system of nerves

diameter = 10-80 μm

runs full length of muscle (origin to insertion)

10% body weight

striated

mononucleated

involuntary movement

gap junctions allows signal transduction

50% (?) of body weight

no striations

mononucleated

involuntary

found in walls of hollow organs & skin

(ie. piloerector muscles)

• the contractile element of a muscle fiber
• analogous to an organelle
• composed of sarcomeres

contractile unit of a muscle fiber

Z disc, I band, A band, M band

actin filaments

myosin filaments

[image][image]

anchor point for actin

made up of protein & connective tissue

light band

only actin is present in this area

between I band

area where actin & myosin overlap

area where myosin is located only

no overlap

thin filaments/light band

attached to Z disc

3 components: F actin, tropomyosin, troponin

double stranded helix

active sites that interact with myosin cross-bridges

double stranded helix

physically covers F-actin active sites in resting state

3 globular heads

each head has an affinity for actin, tropomyosin, and Ca²⁺ ions

• thick filaments
• "bidirectional" from M line
• cross-bridges made up of an "arm", hinges, & globular myosin head
• myosin head has ATPase activity

ATP -> ADP + Pi

(releasing energy)

chronic disease

demyelination of white matter in CNS

Multiple Sclerosis

Etiology

viral infection

other environmental factors

overall: unclear

Multiple Sclerosis

Pathogenesis

• autoimmune disorder
• attacks myelin surrounding nerve fibers
• genetic predisposition

Multiple Sclerosis

Signs & Symptoms

• plaques (scarring) accumulating in brain & spinal cord
• symptoms result from deterioration of myelin sheath
• weakness, numbness, vision/balance loss
• bladder/bowel dysfunction, paralysis

Multiple Sclerosis

Complications

• due to loss of neurological function
• recurring UTI, constipation
• muscle atrophy, ventilatory problems
• loss of bone density
• depression, anxiety, paralysis

Multiple Sclerosis

Treatment

no cure

• steroids, interferons
• physical therapy, counseling
• exercise, healthy diet

goals

• hasten recovery from attacks
• reduce relapses
• slow progression

• rare genetic muscle disorder
• triggered by anesthetic agents
• uncontrolled release of Ca²⁺ from SR

Malignant Hyperthermia

Etiology

• autosomal dominant
• skeletal muscle result in massive muscle contraction
• rapid rise in body core temperature
• triggered by volatile anesthetic agents &/or depolarizing muscle relaxants

Malignant Hyperthermia

Pathogenesis

• genetic mutation
• altered ryanodine receptor
• release of Ca²⁺ or prevent reuptake of Ca²⁺ from sarcoplasm
• uncontrolled muscle contraction
• rapid rise in body temeperature

Malignant Hyperthermia

Signs & Symptoms

• increased cellular metabolism, muscle rigidity, heat production
• fasciculations - cause areas to have "dimples"

Malignant Hyperthermia

Complications

• circulatory & respiratory collapse
• death

Malignant Hyperthermia

Treatment

• cessation of use of triggering agent
• cooling of body
• intravenous dantrolene

calcium channel blocker

used to treat Malignant Hyperthermia

Muscular Dystrophy

Duchenne

Becker

Duchenne MD

severe, progressive, X-linked, inherited condition

progressive degeneration of muscles (especially pelvic & shoulder girdles)

Becker MD

milder form

Muscular Dystrophy

Etiology

• coded by gene on X chromosome
• links sarcolemmal cytoskeleton to extracellular matrix
• mutation of this gene leads to muscular dystrophy

Muscular Dystrophy

Pathogenesis

dystrophin-deficient muscle fibers exhibit:

• increased osmotic fragility
• xs influx of Ca2+
• release of creatine kinase (muscle enzyme)
• muscle cell necrosis

continuous efforts to repari results in progressive fibrosis

Muscular Dystrophy

Signs & Symptoms

• increased serum creatine kinase levels from birth
• clinical weakness by age 3 or 4
• develop pseudohypertrophy of calf muscles

Muscular Dystrophy

Complications

• severe muscle weakness
• contractures
• postural abnormalities
• age 10: wheelchair-bound
• age 15: bedridden
• respiratory, cardiovascular, digestive problems
• mild mental retardation

Muscular Dystrophy

Treatment

no treatment, no cure

• moderate excercise
• physical therapy
• respiratory & GI care
• orthopedic surgery may increase quality of life

acquired autoimmune disease

• circulating antibodies bind to ACh receptors at neuromuscular junction (NMJ)

Myasthenia Gravis

Etiology

initiating cause: unknown

infection & drug interaction may be involved

Myasthenia Gravis

Pathogenesis

autoimmune attach on ACh receptors of motor endplates

• results in reduced # of receptors
• thymus plays important role
• T lymphocytes activate B lymphocytes to produce antireceptor antibodies

Myasthenia Gravis

Signs & Symptoms

• muscle weakness & fatigability
• often concentrated in facial muscles
• ptosis, diplopia, dysphagia
• may involve neck & limbs, respiratory muscles

Myasthenia Gravis

Complications

• myathenic crisis-severe respiratory distress
• problems associated with muscle weakness
• altered appearance
• dental hygeine
• paralysis
• respiratory infections

Myasthenia Gravis

Treatment

• cholinesterase inhibitors
• corticosteroids
• immunosuppressants
• immunoglobulin all have varying effects
• plasmapheresis
• thymectomy

• caused by chemical change in muscles after death
• limbs stiffen, difficult to move/manipulate
• ATP required to cause separation of myosin head from actin filament

***binding of ATP causes myosin head to detach from actin active site***

ATP production halts

thus cannot detach myosin heads from actin

• tissues keep Ca²⁺ sequestered
• then deterioration of tissues eventually occurs
• allows Ca²⁺ to leak out into sarcoplasm
• myosin head released, contraction occurs

the Neuromuscular Junction

motor end plates

• located near middle of muscle fiber (α motor neuron)
• 1 motor end plate per muscle fiber
• action potential travels on sarcolemma in all directions; reaches t-tubules
  

Transverse Tubule System

(t-tubules)

• located directly over Z line
• invaginations of the sarcolemma
• communicate with extracellular space
• filled with interstitial fluid
• AP spreads along t-tubules into interior of muscle fiber; causing Na⁺/K⁺ flux

Sarcoplasmic Reticulum

(SR)

• stores Ca²⁺; thus contains high [Ca²⁺]
• membrane has high voltage-gated Ca²⁺ channels & pumps
• calsequestrin binds Ca2+ to prevent ion difference
• longitudinal tubule
• terminal cisternae

protein located in lumen of SR

• binds to Ca²⁺ to prevent ion difference in SR
  • Ca²⁺ loses its cationic charge, no longer in ionic form

• Fingerlike projections from terminal cisternae of the SR
• increases surface area
• voltage-gated Ca²⁺ channels located here; open & allows Ca²⁺ to flood into sarcoplasm upon activation by AP

depolarization triggers voltage-gated Ca²⁺ channels on SR to release pulse of Ca²⁺ into sarcoplasm

• depletes Ca²⁺ from sarcoplasm
• lasts ~33 msec in average muscle fiber
• fast muscle: very brief pulse

Sources of Energy

(ATP)

Sarcoplasmic ATP

Phosphocreatine

Glycolysis

Oxidative Phosphorylation

provides very little ATP

can sustain contraction for a couple of minutes

provides very little ATP for muscle contraction

can sustain contraction for a couple of minutes

• fast production of ATP
• produces metablic end products
• anaerobic
• difficult to sustain contractions due to lactic acid production

• slow production of ATP in mitochondria
• aerobic
• can utilize fats, proteins, glucose, glycogen
• can supply energy for many hours

• built up if you use all O₂ as fast as it is being delivered to tissues
• end up using O₂ stored in myoglobin
• panting, hard breathing to re-supply O₂

• constant/fixed amount of weight applied
• variable length of muscle contracts
• disadvantage: inertia

• constant/fixed length of muscle
• variable tension
• varying amount of force produced
• can calculate how long Ca²⁺ pulse occurs

Force Generated (mV) v. Time (msec) curve

• Gastrocnemius: increased force/pulse; longer duration
• Soleus: intermediate force; longest duration
• Ocular: shortest duration

Large nerves conduct faster than small nerves

• smaller; innervated by smaller nerves
• more extensive blood vessel supply
• allows O₂ to travel into mitochondria; perform oxphos for ATP production
• more mitochondria
• large amounts of myoglobin
• redder in color

• large muscles
• extensive SR
  • want Ca²⁺ to saturate all troponin complexes for fast contraction
• many glycolytic enzymes
• less extensive blood vessel supply
• not dependent on oxphos
• less mitochondria, myoglobin
• lighter in color

• joint
• part moving may run into part pulling on muscle
• extended to maximum: few heads in position to interact with actin even when next AP arrives
• stretched sarcomeres = decrease in force
• heart contractions depend on length of sarcomeres

• all of the muscle fibers innervated by a motor nerve
• come in different sizes
• small: fine control, fast
• large: slow

stimulating certain number of motor units

controls how muscles contract

• spatial
• temporal
• tetanization

multiple motor unit summation

• increasing # of motor units contracting simultaneously

• increasing rapidity of stimulation of individual motor units
• increase AP frequency until muscle doesn't have a chance to relax
• Tetanization

due to temporal (wave summation)

uncontrolled contraction of muscle

monitors changes in muscle length

tells CNS what our muscles are doing

• a rapid, predictable motor response to a stimulus
• unlearned, unpremeditated, involuntary
• occurs because we have reflex arcs

neural pathway - 5 essential components

• receptor
• sensory neuron
• integration center
• motor neuron
• effector

sensory receptor that monitors the environment

conducts signal