fisologia del musculo

U N I T II

Textbook of Medical Physiology, 11th Edition

GUYTON & HALL

Copyright © 2006 by Elsevier, Inc.

Chapter 6:

Contraction of Skeletal Muscle


Anatomy of Skeletal Muscle

Gross organization:

Figure 6-1; Guyton & Hall


Cellular Organization

Muscle fibers

• single cells

• multinucleated

• surrounded by the

sarcolemma

Myofibrils

• contractile elements

• surrounded by the

sarcoplasm

Cellular organelles - lie between

myofibrils (mitochondria,

sarcoplasmic reticulum etc.) Figure 6-1; Guyton & Hall


Molecular Organization



The Sarcomere

A band

I bandZ disc

sarcomere

thick filament (myosin)

thin filament (actin)

titin (filamentous structural protein)

M line

H zone


“Sliding Filament” Mechanism

Contraction results from the sliding action

of interdigitating actin and myosin

filaments

RELAXED:

CONTRACTED:


F-actin• double-stranded helix

• composed of polymerized G-actin

• ADP bound to each G-actin

(active sites)

• myosin heads bind to active sites

tropomyosin• covers active sites

• prevents interaction

with myosin

troponin• I - binds actin

• T - binds tropomyosin

• C - binds Ca2+

The Actin Filament

− the I band filament

− tethered at one end at

the Z disc

− 1 m long: v. uniform

nebulin forms guide for

synthesisFigure 6-6; Guyton & Hall


The Myosin Molecule:

• two heavy chains (MW 200,000)

• four light chains (MW 20,000)

• “head” region - site of ATPase activity



Mechanism of Muscle Contraction

Theory:

Binding of Ca2+ to

troponin results in a

conformational

change in

tropomyosin that

“uncovers” the active

sites on the actin

molecule, allowing for

myosin to bind.


“Walk-Along” Theory



“Walk-Along” Theory

1. Myosin head attached

to actin

3. Myosin head “cocked”

(ADP and Pi bound)

hydrolysis

4. Myosin head attaches

to new site(ADP bound)

Pi

2. Myosin head releases(ATP bound)

ATP

POWER

STROKE

ADP


Rigor mortis:

• state of contracture that occurs following death

• due to loss of ATP

RIGOR

ATP1. Myosin head attached

to actin


Muscle Mechanics


Length-Tension Relation for Skeletal Muscle

• Active tension cannot be measured

directly

• What can be measured?

(1) passive tension - tension required to

extend a resting muscle

(2) total tension - active tension and

passive combined

• Active is calculated from 1 & 2

(AT = TT – PT)

• Note that active tension falls away

linearly with increasing length

Length (proportion of resting length)

1.0 2.00

50

100

active tension

passive tension

total tension

Normal operating

range


Length-Tension Relation – The Experiment

100

50

0

0 1x 2x

Length (proportion of resting length)Tensio

n(%

ag

e m

ax c

on

tra

ctio

n)

passive

Passive tension

Zero tension

1

stimulus

2

2

3

3

Total tension active

total

(preload)

(afterload = ∞ )

1


Normal operating

range

Tension as a Function of Sarcomere Length

• Stress is used to compare

tension (force) generated by

different sized muscles

– stress = force/cross-sectional

area of muscle; units kg/cm2)

• In skeletal muscle, maximal

active stress is developed at

normal resting length ~ 2 m

• At longer lengths, stress

declines -

• At shorter lengths stress also

declines -

• Cardiac muscle normally

operates at lengths below

optimal length -

active

stress(tension)

sarcomere length ( m)

0

1

0 1 2 3 4

0.5


Relationship of Contraction

Velocity to Load

no afterload:

• maximum velocity at

minimum load

increased afterload:

• contraction velocity

decreases

contraction velocity is zero

when afterload = max force

of contraction

A

B

A: larger, faster muscle (white muscle)

B: smaller, slower muscle (red muscle)


Types of Skeletal Muscle- speed of twitch contraction -

• Speed of contraction determined by

Vmax of myosin ATPase.

– High Vmax (fast, white)

• rapid cross bridge cycling

• rapid rate of shortening

(fast fiber)

– Low Vmax (slow, red)

• slow cross bridge cycling

• slow rate of shortening

(slow fiber)

• Most muscles contain both types of

fiber but proportions differ

• All fibers in a particular motor unit

will be of the same type i.e., fast or

slow.



• fast and slow fibers show different resistance to fatigue

• slow fibers

– oxidative

• small diameter

• high myoglobin content

• high capillary density

• many mitochondria

• low glycolytic enzyme content

• fast fibers

– glycolytic

• large diameter

• low myoglobin content

• low capillary density

• few mitochondria

• high glycolytic enzyme content

forc

e (

% in

itia

l)

time (min)

50 60

Fast (white muscle)

Slow (red muscle)

Types of Skeletal Muscle- resistance to fatigue -


What do the different types do?

• Fast, slow and intermediate twitch type muscle can be identified by histochemistry.

• In any muscle there will be a mixture of slow and fast fibers.

• Motor units containing slow fibers will be recruited first to power normal contractions.

• Fast fibers help out when particularly forceful contraction is required.

Different people have different proportions of these types.

There is little evidence that training alters these proportions in humans.

Fast-twitch slow-twitch

Marathon 18% 82%

Runners

Swimmers 26 74

Average 55 45

man

Weight 55 45

Lifters

Sprinters 64 37

Jumpers 63 37


Conversion of Fiber Type- fast to slow -

• Anterior tibialis –– Predominantly fast twitch (upper)

– Stains light: few mitochondria

– Few, small capillaries

– Large fibers

• Electrical stimulation (10 Hz) via motor nerve (60 days)

– Stimulating fast muscle at the pace of a slow muscle converts fast twitch fibers to predominantly slow twitch

fibers (lower)

– Stains dark: more mitochondria

– Many, large capillaries

– Larger fibers

left AT

right AT


Motor Unit:

• All fibers are same type (fast or

slow) in a given motor unit

• Small motor units (eg,larnyx, extraocular)

− as few as 10 fibers/unit

− precise control

− rapid reacting

• Large motor units (eg, quadriceps

muscles)

− as many as 1000 fibers/unit

− coarse control

− slower reacting

• Motor units overlap, which provides

coordination

• Not a good relation between fiber type

and size of motor unit

A collection of muscle fibers innervated by a single motor neuron


Force summation: increase in contraction

intensity as a result of the

additive effect of

individual twitch

contractions

(1) Multiple fiber

summation: results from

an increase in the

number of motor units

contracting

simultaneously (fiber

recruitment)

Muscle Contraction - force

summation

(2) Frequency summation: results

from an increase in the frequency

of contraction of a single motor unit



Frequency Summation of

Twitches and Tetanus

• Myoplasmic Ca2+ falls (initiating relaxation) before development of maximal contractile force

• If the muscle is stimulated before complete relaxation has occurred the new twitch will sum with the previous one etc.

• If action potential frequency is sufficiently high, the individual contractions are not resolved and a „fused tetanus‟ contraction is recorded.

Myoplasmic [Ca2+]

Force

APTime (1 second)

Fused tetanus


Muscle Remodeling - growth

hyperplasia

hypertrophy

lengthening

• Hypertrophy (common, weeks)

– Caused by near maximal force development (eg. weight lifting)

– Increase in actin and myosin

– Myofibrils split

• Hyperplasia (rare)

– Formation of new muscle fibers

– Can be caused by endurance training

• Hypertrophy and hyperplasia

– Increased force generation

– No change in shortening capacity or velocity of contraction

• Lengthening (normal)

– Occurs with normal growth

– No change in force development

– Increased shortening capacity

– Increased contraction velocity


Muscle Remodeling - atrophy

atrophy with fiber loss

atrophy

• Causes of atrophy

– Denervation/neuropathy

– Tenotomy

– Sedentary life style

– Plaster cast

– Space flight (zero gravity)

• Muscle performance

– Degeneration of contractile proteins

– Decreased max force of contraction

– Decreased velocity of contraction

• Atrophy with fiber loss

– Disuse for 1-2 years

– Very difficult to replace lost fibers

weeks

months/

years

fisologia del musculo

Documents

actin filament

myosin troponin

myosin molecule

myosin head cockedadp

myosin filamentsrelaxed

actin t

actin molecule

passive tension tension