Skeletal Muscle

Outline

❚ Structure❚ Molecular mechanism of contraction❚ Molecular characteristics of contractile

proteins❚ Interaction between myosin and actin on

muscle contraction❚ Neuromuscular junction

Skeletal muscle

❚ Skeletal muscle makes up 40 % of body mass❚ Smooth muscle, cardiac muscle, make up 5-10 % of

body mass

❚ Skeletal muscle- voluntary contraction, striated, multi-nucleate, terminal cell type

❚ Smooth muscle-involuntary contraction, non-striated, uninucleate, can undergo mitosis

❚ Cardiac muscle, involuntary contraction, striated, uni- or binucleate nuclei, slow dividing, terminal cell type

Nomenclature

❚ Sarcolemma- plasma membrane❚ Sarcoplasmic reticulum- endoplasmic

reticulum❚ Muscle fiber- cell❚ Myofibril-subcellular fibers❚ Sarcomere - functional unit of myofibril

Muscle zones

❚ A band = thick and thin filaments❚ I band = thin filaments only❚ Z line = actin attachment point❚ H band = thick filaments only

Molecular Mechanism of Contraction

❚ Sliding filament theory of contraction❙ Shortening of the sarcomere is caused by

increased overlap between thick and thin filaments, not shortening of thick and thin filaments

Sliding Filament Theory of Muscle Contraction

Optimal overlap between thick and thin filaments

Molecular Characteristics of Contractile Filaments

❚ Myosin (thick filament)❙ actin binding domain❙ ATPase site❙ ATP binding❙ molecular hinges

Myosin:•Actin binding site•ATP/ADP binding sites•ATPase site

Actin (thin) filament

❚ Polymerized chain of G actin - called filamentous actin (F actin). Double helix

❚ tropomyosin- wraps around actin, covers myosin binding domain

❚ troponin- 3 subunits attached at periodic locations along tropomyosin fiber❙ tropomysin binding domain❙ calcium binding domain

Interaction Between Actin and Myosin to Cause Contraction

❚ Pure actin and myosin will bind to each other readily❚ If troponin-tropomyosin complex added, inhibits actin

and myosin binding, therefore active binding sites on actin filament are blocked by troponin-tropomyosin complex

❚ When calcium ions bind to troponin, active binding sites are uncovered and conformational change allows myosin to bind to actin

❚ As sites become uncovered, myosin binds to actin

Cross-bridges on either side of the thick filament face each other.

isometricisotonic

Excitation-contraction coupling❚ All muscle tissue is irritable,ie.,

depolarizes when electrically stimulated❚ Nicotinic cholinergic receptors on the

sarcolemma are ligand-regulated Na+

channels❚ Therefore, when Ach binds, Na+ enters

and muscle depolarizes❚ The motor nerves innervating skeletal

muscle originate in the ventral horn of the spinal cord (somatic motor NS) and are cholinergic

Motor unit=motor nerve and fibers that it innervates. One motor nerve may innervate 100 muscle fibers, but each muscle fiber is innervated by only one nerve

End plate potential

T-tubules

❚ Application of small amounts of electrical current around Z line, but not other areas, is capable of producing a contraction

❚ Anatomical studies in frog muscle indicated a series of sarcolemma invaginations that carry current to inner myofibrils- T-tubules

❚ Each T-tubule bordered on either side by swollen region of sarcoplasmic reticulum, lateral or terminal cisterna(e);together this structure is called a triad

❚ Cardiac muscle similar, 1 T-tubule and 1 lateral cisterna = Diad

AP causes Ca2+

channels in SER to open

Neuromuscular junction

❚ Specialized synapses between cholinergic motor neurons and skeletal muscle

❚ Each motor neuron may innervate 1-100 individual muscle fibers

❚ Each muscle fiber innervated by only one motor neuron

❚ 1 motor neuron and all muscle fibers it innervates is called a motor unit

❚ Acetylcholinesterase- enzyme in the cleft that degrades acetylcholine

Recruitment of Motor Units

❚ Each muscle fiber contracts in an “all-or-nothing” fashion

❚ If so, then how do whole muscles contract in a graded or proportional fashion?

❚ Answer: Differential recruitment of motor units.

Clinical Correlations

❚ Drugs that interfere with neuromuscular junction❘ nicotine- binds irreversibly to nicotinic receptors❘ Acetylcholinesterase inhibitors- neostigmine,

prolonged muscle contraction❘ Curare- poison dart frog skin, blocks Ach

receptors, muscle relaxation❙ Strychnine- inhibits glycine input to motor neurons in

spinal cord. Normally, glycine inhibits motor neurons. Strychnine causes disinhibition of motor neurons, over-activation of motor neurons and convulsions

Clinical Correlations (con’t)

❚ Amyotrophic lateral sclerosis (ALS)- Also known as Lou Gehrig’s disease. Scar tissue forms around motor neurons causing death of motor neurons and muscle weakness. 90% of cases have no cause

❚ Myasthenia gravis- autoimmune disease that attacks muscle nicotinic receptors

ATP conservation

❚ If muscle is stimulated, ATP levels don’t change

❚ Creatine phosphate is a muscle storage form of phosphate

Cardiac muscle