Microscopic Anatomy and Physiology of Muscle

Type 1 muscle fibers

Stain dark

Contract slowly (Slow twitch)

Can contract for longer periods of time

Type 2 muscle fibers

Stain light

Contract quickly (fast twitch)

Susceptible to fatigue

The speed of contraction is related to what?

myosin ATPase

Endurance relates to content and activity of mitochondria

(Generate ATP for contraction -oxidative/aerobic metabolism)

Sustained contractions

slower twitch

Anti-gravity muscles

I bands

Light zones (thin filaments only)

A Bands

Darker regions (thick and thin filaments)

What is the banding pattern of myofibril composed of?

Alternating A and I bands

What Bisects each I band?

Dense Z line

One end of each filament is attached to Z line

What is the Sarcomere?

Myofibril between Z lines

Fundamental unit of contraction in striated muscle (Skeletal, and Cardiac)

Each muscle fiber has how many myofibrils?

100s to 1000s

Each myofibril:

1500 thick filaments

3000 thin filaments (wrap around the thick)

Thick myofilaments are composed of what?

Myosin = gold club shaped protein

thin myofilaments are composed of what?

Actin= globular protein

What functions does the sarcoplasmic reticulum (agranular- lack ribosomes) do?

Excitation (contraction) coupling

What is also found in muscle fibers

Golgi apparatus

many mitochondria

Glycogen (liver has lots of glycogen and Skeletal muscle- whole body)

T tubules are continuous with plasma membrane. What do they do?

Extend into the interior of muscle fibers (at right angle). at myofibrils and sarcoplasmic reticulum

Propagates action potentials from sarcolemma (into interior of muscle fibers=initiate contraction)

Number of muscle cells is what?

Set at birth

increase in muscle mass= hypertrophy (increase in myofibrils and vascularization)

If nerve supply to a muscle fiber is destroyed what happens?

Fibers decrease to almost nothing

Denervation or neurogenic atrophy

Ex. Sweeney Shoulder of draft horses - subscapular nerve damaged by collar → Atrophy of supraspinatus and infraspinatus muscle of shoulder

How is a skeletal contraction triggered?

by an action potential 

initiated by firing of a motor neuron

Axon branched terminated in a neuromuscular junction (mid-point of muscle)

What is a type of excitatory synapse?

Neuromuscular junction

What is the receptor for skeletal muscle contractions?

nicotinic acetycholine receptor

What is resting membrane potential?

-70 mv

What cells are excitable?

neuron and skeletal muscle

Action potential is not propagated directly into muscle cell. explain the steps (look at drawing for help)

Depolarization of motor nerve ending releases acetylcholine (chemical neurotransmitter ACH)

ACH diffuses across the junction binds to Nicotinic receptors (key) located on the muscle fiber

Stimulates opening of ligand-gated (lock and key) NA channels→ leads to Na (+ charge) rush into the cell leading to membrane depolarization. 

move 3 sodium out and 2 potassium in

After Ligand gated channels open to start depolarization, what happens next. Explain the steps (look at drawing for help)

End-plate potential =local depolarization of sarcolemma at the neuromuscular junction via ligand-gated channels

depolarization is usually enough to reach threshold potential of electrically gated Na channels (after RMP becomes more positive)

Channels open and more Na rushes in

local current occurs again and other action potentials are generated in adjacent areas

Entire sarcolemma of muscle fibers depolarized

3 step of contractions

T tubules are inward continuations of sarcolemma (action potential travels along tubules throughout fiber)

Some T tubules pass immediately adjacent to SR 

Structural link between: Protein in sarcolemma of T tubule (dihydropyridine receptor) and membrane protein channel in SR

Channel becomes permeable to Ca2+ (because of the link between two proteins)

HAVE TO HAVE CALCIUM BEFORE A CONTRACTION

Last step of contractions

Ca2+ concentration in SR is greater than sarcoplasma (100-fold greater)

Ca2+ diffuses into sarcoplasma and into myofibrils

Increase in Ca2+ in myofibrils leads to interaction between thick and thin filaments

Movement (sliding) of thin past thick towards center of sarcomere

Shortens the sarcomere→ Shortens myofibrils→ entire muscle

Hyperkalemic periodic paralysis (HyPP) (Increase in Potassium)

Genetic Disorder of horses

Genetic mutation of transmembrane protein (Electrical gated Na channel is defective) Increase permeability to Na→ depolarization →involuntary muscle contractions

Hyperkalemia is increasing serum K

Clinical sign: muscle spasm, tremors, sweating, and weakness

Thick filaments is a bundle of what?

Myosin and it has two parts:

Filament like part (lies parallel to similar parts of myosin, and makes up the length of filament)

Projects out like an arm from end of filament- enlargement at end is myosin head

Thin filament is made up of three proteins. What are they?

Actin (most prominent, 2 strands wound around each other)

Tropomyosin (2 strands wound around each other, and spiral around actin)

Troponin (bound to tropomyosin at specific sites, together called troponin-tropomyosin complex)

Relaxation

Contractions happen as long as there is excess Ca2+ in the sarcoplasm

When effect of action potential on sarcolemma ends:

Ca2+ goes back into SR

Ion pumps in membrane of SR use ATP to pump Ca2+ (for storage until next action potential) without ATP muscle cannot relax

When most Ca2+ is removed, thick and thin filaments are dissociated

Allows elasticity of muscle to return to resting length (pulls Z lines and thin filaments back to original position)

What is sign of heart attack?

Troponin in bloodstream

Ca2+ binding sites binds to troponin

What is vital for the continuation of contractions?

ATP and Ca2+ level in sarcoplasm

Curarifrom drugs

Bind to ACH receptors so ACH can not bind to them→ no end potential (Stop at step #1 and 2 of contraction)

ACH-ase does not break down curare

Death from asphyxiation

dose dependent

medically used for some surgeries

Drugs that affect skeletal muscle function: Botulinum Toxin

Very early

Prevent release of ACH

→ prevents no action potential= flaccid paralysis

“limberneck” in poultry

Tone

slight tension muscles exhibit when at rest

continuous transmission of impulse at very low frequency

Keeps muscles in partially contracted state

prevents them from become flaccid (flabby)

When an animal gets excited (anxious, fear, etc.) what happens to muscle tone?

Muscle tone intensifies

Animal can respond faster to stimulus

Seen as skittish (jumpy)

Describe muscle tone during sleep.

Tone is low allowing for optimal relaxation

Describe smooth muscle

Involuntary muscle

99% is visceral type (organs)

AKA single unit or unitary smooth muscle

Joined by gap junctions

1% multiunit smooth muscle

Gap junctions not prevalent (pilomotor muscles)

Smooth muscle Structure

Fusiform (spindle shaped)

Central nucleus

Mostly sarcoplasm (no striations, myofibrils, or sarcolemma visible w/light microscope)

filaments with actin and myosin, not orderly arrangement (no shortening of sarcomere)

Increase hypertrophy and hyperplasia (mitotically) Uterine wall during pregnancy

Smooth Muscle Stress-Relaxation (plasticity)

Adjust to stretching w/o increasing final tension

Tension increases with stretching-at first

Relaxes to original tension 

Ex. stomach- filling with food, SI- Food moving along, Blood vessel when blood volume increases

Allows expansion w/o pain, and not loose contractility

reverse when stretch is reversed (empty urinary bladder)

Smooth muscle contraction (slower than skeletal)

cause of contraction/relaxation variable

less cell energy

Role of calcium in smooth muscle contraction

contraction/relaxation related to Ca2+ concentration in sarcoplasm

some Ca2+ stored in SR, but also have Ca2+ channels in outer membrane

Voltage gated/ligand-gated channels

respond to hormones

Ca2+ channel blockers (useful for reducing blood pressure)

When Cytoplasmic Ca2+ increases → binds regulatory protein (calmodulin) when bound to calmodulin, activates a kinase—> phosphorylates myosin results in contraction

Relaxation occurs by Unphosporylation by enzymes in cell (occurs when Ca2+ is reduced (Ca2+ Atp-ase)

Sympathetic Epinephrine and norepinephrine bind B2-adrenergic receptors

Effect: relaxation of smooth muscle cells

ex. airways

Sympathetic epinephrine and bind a1-adrenergic receptors

Contraction of smooth muscle cells

ex. blood vessels

Parasympathetic Acetycholine bind muscarinic ACH receptors

Contraction of smooth muscle cells

ex. SM of airways and blood vessels

Cardiac muscle (involuntary striated)

Striations fainter than muscles

Major difference

Heart made up of different cells (than muscles)

muscle cells meet end to end= intercalated disks

Excitation and Contraction of Cardiac muscle

Do not require nerve stimulation

BUT action potentials must occur on cell membrane → 1st occur spontaneously= specialized myocardial pacemaker cells

Cardiac action potential slower than skeletal muscle

Contraction lasts as long as action potential does

Ca2+ binds to regulatory proteins on actin filaments

Cardiac Hypertrophy (increase in cell size)

When heart has excessive work to do

Do NOT regenerate or undergo hyperplasia (similar to skeletal)

Living in high altitude can cause hypertrophy (increase vascular resistance, increase blood pressure in lungs)

Brisket disease (high mountain disease) in cattle

Hypertrophy can NOT compensate for increase in vascular resistance

clinical sign= edema of brisket