macontraction

I
-> cross
bridge formation
fo
AP musch
ta t come to

in
/ ->
depolarization down titubules

-> Cat release from SR .

-> Ca2t conformational change in

tropomyosin
↓
exposes myosin binding sites

⑰ myosin binds actin

-
-
cro
redsnor
-
0⑧
D
ADP-P bound

for
:

to myosin
 traction
② myosic changes

I
cow
8
00
conformation
ADP+ P : neleased /

③ myosin
detaches
000
As binds to
⑧
myosin -

④ changes
-

myosin
t
conformation
008
high energy
O
ATP hydrolyse -
Ho ADP +
Pi
 -
I
o -

D
geen
-
S
--
->
-

000
.
O
0
00 ene muscle fiber
Opj80 tons of
myofbrils
m
-

0
o
-
me
-
-
-
One
musch
made up of
a lot of
musche liber
 -
-
>
Calcium is re-uptaken into the t-tubules as contraction ends

->
S

LioniT

C
pr
 Termination of contraction requires re-
uptake of Ca2+ into the sarcoplasmic
reticulum

⑳
Exchange
Three mechanisms:
↳Naat
1. extrude Ca2+ using an NCX pump
2. extrude using a PMCA pump (plasma
- membrane Ca-ATPase).

-
3. Ca2+ re-uptake by the sarcoplasmic
reticulum using -
a SERCA pump
(sarcoplasmic and endoplasmic
reticulum Ca-ATPase)

Extrusion would eventually totally deplete

the cell of Ca2+ and is therefore a minor
=-
mechanism

Most is Ca2+ re-uptaken into the

-
sarcoplasmic reticulum.
 Lat
Cartist
Cart
Cart Ca
at

n ↓ groent
mor
Cat
as ho

Nat m
tra
* ..

SR
Lat
Cant ons
Na Nat Wat
concentrati o n
9 L/s
Na down
Nat roc
en

E
-

↓
uses
this loss of
potential energy
Cait
to carry
What about death.. Where you you get stuck?

mortis
in
rigor
at
-> muscle stay
where Ayosin
phase
El actin are
bound

-> so the muscle can't

be moved ,

-
↓ pen
What about cramps?

Skeletal muscle cramps may be caused by

- Lack of electrolytes (sodium, potassium,

or magnesium.
- Muscle fatigue (lack of ATP)
--

- Continuous innervation of muscle

Lack of electrolytes

Contraction stops because of re-uptake of

calcium into sarcoplasmic reticulum
Too little magnesium also causes cramps cause
Mg2+ acts as a calcium blocker, inhibiting calcium
release from the sarcoplasmic reticulum

Without enough Mg2+, too much Ca2+ released or

too long

↳ L
deweg ulation of
Care handling
If Ca2+ is not >reuptaken, then tropomyosin does
not inhibit actin binding

⑧
I
Muscle fatigue (lack of&
ATP)

Lack of ATP generation can cause myosin to stop in

bound position
-

ways to make
ATP .

Disease of metabolism can lead to tendency to

cramps during vigorous exercise
• #Glycogen metabolism (McArdle’s or Tauri’s
-

disease)
• Fatty-
m

acid oxidation (patients deficient for carnitine

-

palmityl transferase)
-
Continuous innervation of muscle

Any local irritating factor (metabolic abnormality, severe cold, lack

of blood flow to the muscle, over-exercise) can elicit pain or
similar sensory impulses

Transmitted from the muscle to the spinal cord through pain

reflex.
Pain reflex muscle contraction.

The contraction in turn stimulates

the same sensory receptors still
more, which causes the spinal cord
to increase the intensity of the
contraction still further.
So why stretch when you have a cramp?

Reciprocal inhibition
• Purposely contracting the
muscle on the side of the
joint opposite to the
cramped muscle while
preventing movement of
the joint (isometric
contraction) causes
reciprocal inhibition
• Fact that every muscle has
an “opposite” muscle that is
forced to relax when the
other side activates
Stretching also physically prevent actin/myosin from
interaction (or reduces it)
Review Question
1) What is the difference between isometric and
isotonic. Explain, but also draw the tension/time
curve.

2) What is tetanus? How do you reach tetanus?

-

⑩
3) Explain actin-myosin cycling. tibubules
sit
4) What is the role of the t-tubule?
-> same
length different forc

L
en
->
same force , different lengt

force
L
--
tu
-Ill
-
↓

!
Hetanu

-
H

MX
M
--
...
① Myosic
do adten

& Myosin head bends

-> ADP- Pi Leave
weds
↓ ATD
③ Myosin detaches

④ myosic neturns to high

energy form
uses hydrolysation of
ATP .
 I

O
·Meer
B ee
I
ana
a

-
->
depolarization travels therough a

network tubele
 S

Three things affect force generation:

ia He
how active
1) Frequency of stimulation about
Summation of twitches musch
is
explain
-7
Creation of tetanus but
doesn
betweem
and
differencmuscle
->

on ther
2) Fiber diameter

Ge
ano
a Each muscle is made up of myofibrils
No. of thick/thin filaments per cross sectional area does not change muscle
4πr2
· So overall diameter defines force that can be generated.
Larger diameter, more cross bridges, more force.
4r2 =

3) Change in fiber length

Fiber length itself does not affect force
Length compared to resting length affect force generation
 Stretched muscle, few of
the actin-myosin in
contact, little force
generation

0
Shortened muscle,
overlap of thin filaments.
Not all crossbridges can
be made.

Skeletal muscles are

0 contrained by bones to
operate in the maximum
force generation region.

-
-N
- (
d

D
o
 -

Force generation by whole muscle

oo
8 0
0
-
How do you create different strengths of muscle contraction?

Summation – 5x difference

Motor units
- One motor neuron can synapse on more than one muscle
- All fibers of one motor neuron called a motor unit
- Not all motor units are the same size.

-> number of
- Fibers

diameter libers it
->

of muscl

innervates .
 O
/
-

--

0 :
&

-
Large motor units – more force
Small motor units – more precise movements

Small force needed, activate small motor units

- As you need more and more force, you recruit larger and larger motor units.
The order of recruitment is called the ”size principle”.

D
- Motor units that are not activated slide along each other without creating cross

0
bridges
-
- So no force generated.

E
Not only motor units vary in number of muscle cells. The motor neurons
themselves vary in size too
smo
- Wilt -

lange
-h
- (II((((((((() -
->
Larger diameter neurons are hard

⑧ 0
to depolarize
-

⑧D
Stronger signal needed to activate
them.

So with gradually increasing

-
synaptic input
- Smaller motor neurons fire first
- Larger motor neurons fire only
with more activity
 -
syp I
Speed of contraction
Time
↓ ↓
Speed of contraction can
differ between muscle cells

When stimulated, muscle cell

④
do not all dake same amount
of time to reach their peak;

Muscle can be classified into

↑ 1) Slow twitch fibers
-

2) Fast twitch fibers

-

Ondert
ondatI

gict
↑ dow
:

ATD last
use

quck's
more
Difference is due to the type of myosin

Slow myosin
- -

Fast myosin
-

Difference in reaction rate for hydrolysis of ATP **

P+ Pi
*
A

Slower hydrolysis means slower force generation

-

Faster ATPase means more bridges formed per second.

usterst
 anderba
o
inc
Energy usage
->
nooyse
Each cross brdige formed requires*
one ATP
-
Energy requirements are therefore very high aggen
-

ATP can be produced by two methods

aerobic
with
->
1) Glycolysis (anerobic)
2) Oxidative phosphorylation (aerobic)

san LIAD
-

Ee
Fat
n -

-
-
-

->
S

proden De
&e
Or
-
- 0
 -> lactic
>- sugar

1
and

I
lucose ->
glycolysis
ethera
- ↓
o
El
lactic
and
E
pyruvate
-> etharal
- sugar .
 P
-
⑱ee
Oxidative phosphorylation requires a lot of O2.

At peak activity oxygen cannot diffuse to muscle fibers fast enough.

->
1) Glycolytic fibers
- Low capacity to generate ATP from oxidative phosphorylation
O
o
- Few
- mitochondria
- Large diameter ”White” muscle

-Aerobic
mechanism
2) Oxidative fibers
- Many mitochondria
-
- Large capacity for oxidative phosphorylation
- Many blood vessels in muscle
o
-
E o
- Cells are smaller diameter (less distance for O2 diffusion)
- Also contains a protein called myoglobin -
or
- -
”Dark” muscle O-
 glucose
pyruvat
↓
CoA
Acetyl

W
02 02

De On
On
1) Glycolytic fibers
- Large diameter/high force
- Bursts of energy
- In chicken, breast.. Don’t fly most of the time (white meat)
- In humans, sprinting

2) Oxidative fibers
- Endurance muscle strength
- In chicken, legs.. Dark meat
Review Question
1) Why does a muscle generate different amounts of
force at different % resting length?

2) Explain what a motor unit is and how they are

recruited as you build force.

3) Explain why metabolism of muscle cells affects the

type of force they make. How can you tell these type
of cell from each other?
 # ogloby
n

4 kame
groups
met
.

in
lobin

⑧E
·
hemoglobin - i

lob I

andertu
home
myo S
in ->
grou

--
i
be
- -

l -> -E ... -
. .

re
I
Fp-y
-
Creatinine
-

-Phosph
My
-
Er
⑳
P+Pit AiD
11 ru S Cr
ATP -
AT
CrP
ATP - L
-
ADP-PCr PCr+ ADP AMD
ATP
=

- i -
-
slaw - -xdate
=>
muscle control

-
-L posture
movement
eye
-

E
fast ->
fast oxidative
mather running .

fast
- glycolytic
-
e

->

sprint-
Three types of muscle cells
o
-
-

- Skeletal muscle ->

-

-
-

I
-

heart --

- Cardiac muscle
O
->
- -
-

- Smooth muscle (around organs)

-
-

0 S
-

-
-

stricted muscle
-

>
↓

organ
-
cardial
--
On 0
-

on
⑧
- -

⑳
-

⑦ -

y
-
-

S
- --

i
-
- -
-

I
-

W -
-

&
n

--

.
8

- -

- &
-

muld nu elected
stell stricted .

-
ee
YY
=-
-

-
/
-

↳
 Multiple functions:

Stomach, helps break down food

Blood vessels, regulates flow through

vessels.

au tonomic nervors

system con

Smooth muscle .

ielate
Abrow ↓
Also an important therapeutic target:
• Bronchiodilators target smooth muscle in lungs.
• Metoclopramide
- E
(anti nausea) can stimulate and promote gastric emptying
by increasing smooth muscle signalling

E
Control by endocrine system (hormones, chemical factors) much more than
skeletal system.
cadia?
of
actuatiosystem
n
contract
independent
.

-> andocrin modulati

Smooth -> both modulate & activate </pervor

- I
Different patterns of contraction for different smooth muscles
-

-
↓
- Steltal
than

musce

-
-
relax
Sphrincters ->

when activated
↑
E
--
 - ove
lager of neurors

spreads all of
te
layers
Single-unit smooth muscle: smooth muscle cells .

• Smooth muscle cells are electrically coupled such that electrical stimulation of one cell
-

is followed by stimulation of adjacent smooth muscle cells.

• Results in a wave of contraction, as--
in peristalsis

C
I
o
:* 2
C

Multi-unit smooth muscle:

• Multiunit smooth muscle cells are not electrically coupled, so stimulation of one cell
does not necessarily result in activation of adjacent cells.
• E.g. iris of eye
 skeletal only somatic
->

smooth
Innervation .
-only autonomic

•&
Arteries/arterioles are innervated only by
E sympathetic nervous7
system
-

- -
• Other tissues, both sympathetic and parasympathetic innervation.

• Gastrointestinal has its own nervous system, the enteric nervous

& system, that innervates the smooth muscleT
↓
moru
-

-
• Some organs, like the uterus, are not innervated at all.

Etated
- -

by
prrels
hormones
Differences with skeletal muscle:

1. Smooth muscle can contract on all axis.

• Thin and thick filaments are not aligned so smooth muscle is not
striated
-
excitable all
2. Smooth muscle can be activated by autonomic neurons, but also has spontaneous
by circulating factors/hormones (e.g. adrenaline), pacemaker
hypepolarization &
activity, and a variety of drugs. de polarization
-
· in I
I
-
03. Calcium comes both from sarcoplasmic
reticulum and from extracellular calcium
(pumped in over membrane)
• Smooth muscle cells also lack T tubules that
provide electrical links to the sarcoplasmic
reticulum.
• Diagram shows 3 sources of calcium (two
extracellular and one intracellular) and 2

S So
ways calcium levels are returned to normal
(pumped out, returned to sarcoplasmic
reticulum).

za
two pu
-

⑧4. Don’t necessarily need a change in membrane potential to cause contraction.

Compounds that increase intracellular Ca2+ and can cause contraction without changing
the membrane potential.
 -
hormone or
compound can

⑰ cause
begand I
ate

Cat to
-Late open

↓
·

Een
3. Smooth muscle cells lack T tubules that provide electrical links to the
sarcoplasmic reticulum.
Skeletal muscle does not require extracellular calcium, but smooth muscle cells
do.
4. Don’t necessarily need a change in
membrane potential to cause contraction.
Compounds that increase intracellular Ca2+
and can cause contraction without changing
the membrane potential.

mosin He
5. Contraction is not initiated by binding of
Ca2+ to troponin. Smooth muscle cells have
->

no troponin. Requires the phosphorylation of enzyr

the=light chain of the>myosin molecule. mick

Zorg
• When Ca2+ concentration decreases, MLCK I
becomes inactive and the cross-bridges
are dephosphorylated by myosin
phosphatase.

Eeck
S
kinase that adds phospho group
->
enzyme a

L
L

phosphatese - remore a phospho

group

Protecte -> sat

up prote-

polymerase -> make chairs .

->

tropomyosin -> Skelefel

" I
wo binding sites
for sketel
myosin

Autin

⑨ ATB
--
g

is ↳
Upi i

Guaum
au
regent
.

mick
andswher car

is
->
two forms for smooth
musch Imy o sin

b
⑤
~

⑳ D

~Phospho
inactive active

every point along

- >

actin/myosin
cross
bridge Countr
you can
scycle to

in active form .
 Can remain contracted for extended
periods at low levels of energy
consumption.

Change in cross-bridge cycling

kinetic such that the smooth muscle
can maintain force at low energy
cost.

Important for maintaining blood

pressure.

The continuous partial activation of tonic smooth muscle is not associated with action potentials,
although it is proportional to membrane potential.
For smooth muscle cells that must contract for
long times..

Dephosphorylation of a cross-bridge during a cycle

by a constitutively active myosin phosphatase
(black arrows) slows cycling rates and produces the
latch state.

D
In black circle, the time in
force generating
conformation is longer.

300-fold less ATP than

would be required by
skeletal muscle to
generate the same force.
-
⑥
forces ,

Smooth muscle has ability to shift the length-

0 tension curve, depending on the resting
length.

If smooth muscle is stretched/shortened, the

length-tension curve will shift over the course
of tens of minutes to hours.

Termed “length adaptation.”

Molecular basis involves an alteration in the

number of contractile units in series.

to blood
2 .
9 .
t chronic changes
flow
or stretching of stomach
with obesity .
 carand
ac
19
Review Question vorwe eehannels -

I C

1) Why doesn’t smooth muscle cell need an action

potential to contract.

2) How does calcium initiate contraction? Why is no

troponin needed?

3) Explain what the “latched” state is and why it requires

less energy. Why don’t other muscle use it?