Lecture 22

C2006/F2402 '14 -- Outline for Lecture 22

(c) 2014 Deborah Mowshowitz . Last updated 04/20/2014 09:30 AM.

Handouts 22-A -- Smooth muscle innervation & contraction, and Skeletal muscle structure
22-B -- Skeletal muscle bridge cycle & 3 types of muscle
22A & 22B are on Courseworks, because they contain copyrighted material. You can pick up paper copies on the 7th
floor of Mudd after the lecture. You can get pictures of all the structures mentioned using Google Images.
You also need Handout 21C & D
Useful Web Sites & Animations (See also the web-sites page.)
Actin-myosin crossbridge. Watch the myosin head swivel, attaching and detaching from actin. From San Diego State
University.
Muscle structure and contraction There are other videos by this author at
http://www.physioviva.com/animation_list.html and at http://www.youtube.com/user/llkeeley?feature=mhee
Please let me know if you find any of these (or any other animations on these topics) especially helpful. Also let me know if any of
these links do NOT work.
For all the biology related videos of Khan Academy, go to https://www.khanacademy.org/science/biology -- there are videos on
muscle contraction and many related matters.
For additional pictures (& an explanation) of the material discussed below, go to
http://mollythrodahl.wordpress.com/2012/02/28/skeletal-muscle-physiology/

I. How does a nerve or hormonal signal produce an effect, cont? This is material that was
accidentally omitted from topic III of the notes for Lecture #21. It provides backup to the diagrams
on handout 21B. This material (Topic I) was covered last time and will not be reviewed in #22.
A. General solution -- signal triggers an effect in a target tissue (an effector) -- muscle contracts, gland secretes,
etc. Some examples of how this works were discussed in Lecture #21. Below are more details.
B. The Problem -- One signal molecule (hormone, transmitter, etc.) can produce different effects on different
target tissues such as different smooth muscles or skeletal muscle vs. smooth muscle.
C. Two Basic Methods -- See Handout 21B. This topic was included in Lecture #21, in III-C, but this is a more
complete version.
1. Using the Same Receptor & same signaling pathway, but different Target Proteins (or genes)
a. Previous examples:
(1). Insulin effects on skeletal muscle vs liver -- Insulin activates (&/or inhibits)
different target proteins in the two different tissues
(2). Estrogen effects on uterine tissue vs breast tissue -- Estrogen receptor/TF
affects transcription of different genes in the two different tissues (because of
different proteins that affect the action of the TF differently in the two cell types).
b. A new example: epinephrine (epi) effects on two types of muscle
(1). In skeletal muscle: epinephrine causes glycogen breakdown (as explained
file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

previously).
(2). In smooth muscle of lung: epinephrine causes muscle relaxation.
c. Why does this make sense?
(1). Epinephrine (also called adrenaline) is produced in response to stress.
(2). In response to stress, need to "mobilize" glucose -- release it from storage
so it can be broken down to provide energy. Therefore need to increase glycogen
breakdown (and decrease glycogen synthesis) in muscle (& liver).
(3). In response to stress, need to breathe more deeply. Therefore need smooth
muscle around tubes that carry air (bronchioles) to relax.
d. How is this possible? Same receptors, same 2nd messenger (cAMP) are used.
e. The solution: Different target proteins. PKA is activated in both skeletal and smooth
muscle. However the target proteins available to be phosphorylated are different in the two
tissues. Therefore different proteins are phosphorylated and activated (or inactivated) in the
two different tissue types.
(1). In skeletal muscle -- PKA phosphorylates (& activates) the enzyme
phosphorylase kinase, which in turn phosphorylates (& activates) the enzyme that
breaks down glycogen to release glucose. See texts for more details. (Becker, fig.
14-25 or Sadava fig. 7.18 (7.20)
(2). In smooth muscle surrounding the bronchioles -- PKA phosphorylates a
protein (MLCK) needed for contraction, inactivating it. Therefore contraction
cannot occur.
2. Using different receptors & second messengers in different cell types
(See Becker fig. 14-24 (14-23). An example -- effects of epinephrine (adrenaline) on smooth muscle.
Some smooth muscles relax, and some contract in response to epinephrine. In this case, different receptors
& 2nd messengers are involved. How does this work? See below.
Try problem 6-11.
D. Example of Using Different Second Messengers (& Different Receptors). Details of examples on handout 21B.
1. The phenomenon:
a. Epinephrine (secreted in response to stress) has different effects on different smooth
muscles:
(1). On some smooth muscles, epi contraction

(2). On other smooth muscles, epi relaxation (as above)

b. How does this make sense?
(1). In peripheral circulation -- smooth muscles around blood vessels (arterioles)
contract, diverting blood from peripheral circulation to essential internal organs
(2). In lungs -- smooth muscles around tubes carrying air (bronchioles) relax, so
file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

lungs can expand more and you can breathe more deeply.
2. How Ca++ fits in:
a. Ca++ stimulates muscle contraction.
b. To give contraction: Epinephrine binds to receptors on some smooth muscles (ex: around
arterioles) Ca++ released from ER intracellular Ca++ up stimulates contraction.
c. To give relaxation: Epinephrine binds to receptors on some smooth muscles (ex: around
bronchioles) phosphorylates protein needed for response to Ca++, preventing response.
3. Role of receptors
a. Two basic types of epinephrine receptors -- called alpha and beta adrenergic receptors
(adrenergic = for adrenaline). The two types are distinguished (primarily) by their relative
affinities for epinephrine (adrenaline) and norepinephrine (noradrenaline).
b. Some types of smooth muscle have mostly one type of receptors; some the other. (See
table below and table in previous lecture for details of receptor properties.)
c. Two types of receptors activate different G proteins and generate different second
messengers. (Details next time.)
(1). Beta receptors G protein of one type (Gs ) activates enzyme (Adenyl
cyclase) second messenger (cAMP) PKA
(2). Alpha 1 receptors different G protein (Gp ) activate different enzyme
(phospholipase C or PLC) different second messenger (IP3) binds to
receptors on ER membrane opens Ca++channels in ER Ca++ release from
ER contraction
4. How does this all work to allow appropriate response to stress (epinephrine)?
a. Beta type receptors. Beta receptors are found in lung tissue in smooth muscle surrounding
bronchioles.
Stress (pop quiz, lion in street, etc.) epinephrine muscles relax bronchioles dilate
deeper breathing more oxygen energy to cope with stress.
b. Alpha type receptors. Alpha receptors are found in smooth muscle surrounding blood
vessels of peripheral circulation.
Stress epinephrine muscles contract constrict peripheral circulation direct blood to
essential organs for responding to stress (heart, lungs, skeletal muscle).
To review effects of different receptors, try problems 6-21 & 6-22.
5. Medical Uses of all this.
Epinephrine can be used during an asthmatic attack to relax bronchi and ease breathing. Overuse of this
type of broncho-dilator eases breathing temporarily but masks underlying problem (inflammation of lung
tissue) and can have additional serious long term effects (from overstimulation of heart which also has
beta receptors). Heart and lungs have slightly different types of beta receptors, so drugs (agonists) have
been developed that stimulate one and not the other (unlike epinephrine). Many drugs are either agonists

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

or antagonists of signaling molecules such as hormones, transmitters, etc.

Try Problem 6-8 & 6-9 if not yet. (To review agonists & antagonists.)
6. Summary of epinephrine effects on smooth muscle (in lung vs peripheral circulation). See also handout
21B.
Effects of Epinephrine on Smooth Muscle
Receptor Type

Alpha 1 adrenergic**

Beta adrenergic

Receptor binds

norepinephrine> epinephrine

epinephrine norepinephrine

G protein activates

PLC (phospholipase C)*

adenyl cyclase

2nd Messenger

IP3

cAMP

Effect of 2nd messenger

Ion channel in ER opened

PKA activated Ca++ response blocked

Effect on Ca++

Ca++ released into cyto.

None (in bronchioles)

Effect on smooth muscle Contraction

Relaxation

Tissue involved

Peripheral Circulation (arterioles)

Lungs (bronchioles)

Final Effect

Blood directed to central organs

Breathing easier

Note: There are more than two types of epinephrine receptors on smooth muscle cells, so epinephrine may affect
smooth muscle in other tissues in other ways. (There are subtypes of alpha and subtypes of beta.)
* Details of how PLC generates IP3 are in texts and on handout 21A.
** Not all alpha receptors use IP3.

II. How Nervous System is Organized (Handouts 21C & 21D)

A. How is NS organized overall? See handout 21C top, or Sadava fig. 47.1.
1. CNS = brain + spinal cord
2. PNS -- Names of Divisons
a. Afferent vs Efferent.
(1) Afferent = carrying info into the CNS
(2) Efferent = carrying info away from the CNS
b. Efferent subdivided into: Somatic vs autonomic
(1) Somatic = controls skeletal muscle
(2). Autonomic = controls everything else
c. Autonomic subdivided into: Parasympathetic (PS) vs Sympathetic (S)
Try problem 8-8, part I.
B. How do PS and S co-operate? See Sadava fig. 47.9 (47.10). What do they do?
1. What do they innervate?

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

a. Many organs innervated by both

b. Some organs innervated (stimulated) by only one
(1). sweat glands -- S only
(2). tear glands -- PS only
2. What results does stimulation produce?
a. Not always S excites; PS inhibits. Ex: salivation -- S inhibits; PS excites
b. Usually:
(1). S response needed in a crisis
(2). PS response needed in relaxed state. ("para makes you pause")
c. Examples:
(1). S heart rate up; liver releases glucose; bladder relaxes (to hold more) -urination down; digestion down.
(2). PS heart rate down, digestion & salivation up.
C. General Set up of wiring of efferent PNS -- see handout 21D
1. First neuron -- same in Somatic and Autonomic
a. Location -- body in CNS
b. Neurotransmitter -- releases AcCh (Acetyl choline)
c. Receptor -- AcCh receptor (on effector/next neuron) is nicotinic (direct)
d. Effect -- effect of transmitter on next cell is always excitatory (Why? What's the
mechanism?)
2. Second neuron (post ganglionic) -- found in autonomic only
a. Location -- Body in ganglion (outside CNS).
PS ganglion -- Proximal to target
S ganglion -- close to Spinal cord; first neuron is Short.
b. Neurotransmitter
(1). Parasympathetic -- releases AcCh
(2). Sympathetic -- usually releases NE (norepinephrine)
c. Receptor (on effector) -- indirect (metabotropic)
(1). AcCh (cholinergic) receptor is muscarinic
(2). NE (adrenergic) receptor can be alpha or beta (see below & table in
file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

previous lectures) -- 2nd messenger varies

(3). Effect of transmitter on effector -- response of effector can be excitatory or
inhibitory.
Examples: Smooth muscle may contract or relax; heart may beat faster or slower.
(Response depends on type of G protein activated by receptor.)
d. Adrenal medulla
(1). Medulla ganglion -- but neurons have short axons. (Usual 'neuron #2' has long
axon.)
(2). Release neurotransmitter (mostly E = epinephrine) into blood from end of short
axons (within medulla).
(3). Role of E -- 'NT' goes into blood, so E acts as neuroendocrine instead of
neurotransmitter.
Try problem 8-8 part J.
E. Major receptors in the PNS --For details, see summary table in Lecture #20.
1. Acetyl Choline Receptors -- two main types, nicotinic (direct/ionotropic) & muscarinic
(indirect/metabotropic)
2. Adrenergic Receptors -- two main types -- alpha & beta. Both indirect (metabotropic)

II. Muscle Overview

A. Common Features
1. Have actin (MF) and myosin
2. Actin and myosin slide past each other; neither shortens. (For skeletal muscle, see Becker fig. 16-16.)
3. Electrically excitable
a. Stimulus usually generates an AP (in muscle membrane) which then triggers contraction
b. Some smooth muscles respond (contract) w/o generating an AP.
4. Use Ca++ to stimulate contraction
a. Stimulus usually causes a rise in cytoplasmic (cytosolic) Ca ++ in muscle contraction.
b. Details differ: Where Ca++ comes from, what triggers its release, and how it acts, differ in
different muscles.
5. Use hydrolysis of ATP to power contraction.
6. Bridge Cycle -- How the 'sliding' works
a. All muscles achieve contraction (shortening of muscle -- sliding of actin relative to
myosin) by a bridge cycle = cycle of formation and breaking of connections between actin

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

and myosin
b. All use Ca++, actin, myosin, & ATP to run bridge cycle, but details differ.
B. Three main types -- smooth, cardiac and skeletal (See handout 22B for pictures or Sadava Chap. 48 or Becker
Chap. 16. Compare Becker figs. 16-10, 16-22 & 16-23.
The major features of smooth and skeletal muscle are outlined separately below, but actual lecture may skip back
and forth. When doing the problems, consult the handouts on the bridge cycle and smooth muscle contraction
mechanism as needed.
C. Some Major Differences
1. Structure -- See handout 22B
a. Cells Fused?
(1). No -- Smooth muscle -- individual, unfused cells.
(a). Single Unit smooth muscle -- the cells are connected by gap
junctions and contract as a unit -- are electrically coupled.
(b). Multi unit smooth muscle -- the cells are not coupled electrically;
cells are stimulated and contract as multiple individual units.
(2) Functionally fused -- cardiac -- uninucleate but tightly connected at ends
(3) Fused, multinucleate -- skeletal
b. Striated vs. not. How are actin/myosin fibrils arranged? Bundles or sarcomeres?
c. Structure of nerve/muscle synapse.
(1) Somatic Innervation -- See texts for diagram of nerve-skeletal muscle
synapse. Similar to nerve-nerve synapse on handout 20A, but post-synaptic side
is more elaborate.
(2). Autonomic Innervation -- Synapse structure is different -- NT is released
from varicosities, not from special nerve ending. See handout 22A.
Presynaptic Side: Neurons have multiple varicosities (points of contact with
smooth muscle -- contain vesicles of neurotransmitter).
Postsynaptic Side: Smooth muscle has no complex structure at synapse (no
motor endplate). One smooth muscle cell (or group of cells) can get input
from both PS and S.
2. What controls contraction?
a. Skeletal Muscle
(1). Innervated (not enervated) by somatic system (motor neurons)
(2). Receptors: Neurotransmitters at nerve/muscle synapse use nicotinic
cholinergic receptors (direct -- ionotropic).
(3). Source of Ca++: Stimulus (from motor neuron) generates an AP in the
file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

muscle membrane, which causes release of Ca++ from ER. (ER called
sarcoplasmic reticulum or SR in muscle.)
(4). Signal (for contraction) is always excitatory.
(a). Skeletal muscle does get hormonal stimulation (has receptors for
hormones), but hormones do not affect contraction.
(b). Nerve that synapses on skeletal muscle can be inhibited -- in that case,
muscle gets no signal and does not contract. Nerve to muscle can get an
inhibitory signal, but muscle itself cannot.
(c). How are antagonistic muscles controlled? See handout 21C, and 'simple
circuits' below.
b. Smooth Muscle
(1). Innervated (not enervated) by autonomic neurons. See handout 22A.
(2). Stimulus can be excitatory or inhibitory.
(a). Stimulus can be from NT or hormone. Contraction influenced by
hormones as well as autonomic neurotransmitters.
(b). Response depends signal molecule and on type of receptors on
smooth muscle.
(c). Examples
i. Using hormones: epinephrine can cause smooth muscle
contraction (through IP3 in arterioles) or relaxation (through cAMP
in bronchi). See Handout 21B.
ii. Using NTs: In smooth muscle of gut, NE causes excitation
(depolarization); AcCh causes relaxation (hyperpolarization). See
Sadava fig. 48.8 for effects of NT input on membrane potential in
smooth muscle (from GI tract).
(3). Receptors: Neurotransmitters at nerve/smooth muscle synapse use
metabotropic receptors (muscarinic cholinergic or adrenergic).
(4). Source of Ca++: Ca++ to trigger contraction comes from outside cell &/or
ER.
(5). Stimulus doesn't always generate an AP in muscle membrane. If no AP
involved, can trigger release of Ca++ (leading to contraction) by one of the
following:
(a). Graded changes in membrane potential (due to external stimulus or
pacemaker)
(b). Activation of a GPCR by a NT or hormone
(6). Pacemakers? Pacemaker activity, not external stimulus, controls contraction
in some smooth muscles. (See below.)
file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

(7). Has latch state. Unlike striated muscle, can remain contracted longer without
input of ATP.
c. Cardiac Muscle
(1). Contraction controlled by pacemaker cells. (Remember the Loewi
experiment -- isolated hearts beat without any innervation.)
(2). Pacemakers can be speeded up or slowed down by
(a). Hormones
(b). NTs of autonomic NS. See Sadava fig. 50.6 (50.5)
D. Simple circuits -- see handout 21C, bottom or Sadava fig. 47.3 (9th ed only). Integrating sensors, effectors, and
IC (CNS).
1. One synapse, 2 neurons -- monosynaptic circuit -- how sensory neuron signals an effector.
2. Circuit with multiple synapses -- how antagonistic muscles are controlled. For example, when stretch is
detected in a muscle, that muscle contracts and the antagonistic muscle relaxes.
a. Signal to skeletal muscle is always +; a signal (+) means contract; no signal means relax.
b. Signal to neuron (that controls muscle = innervates it) can be excitatory or inhibitory.
c. What makes the (antagonistic) skeletal muscle relax?
Relaxation occurs because the antagonistic muscle gets no signal to contract.
The muscle does not get an inhibitory signal -- it just doesn't get an excitatory signal.
d. Who gets an inhibitory signal? The motor neuron that innervates (goes in to) the
antagonistic muscle gets an inhibitory signal, not the muscle itself. The motor neuron is
inhibited and does NOT fire an AP, so the muscle is not triggered to contract.
e. Terminology -- the term 'innervate' means ' to synapse on' and 'to control'. It does not mean
enervate (decrease the vigor of). Innervate and enervate are completely different in meaning.
3. Role of brain -- adds up/down (as vs. in/out) component
4. FYI: Where is all this located? see Sadava fig. 47.3 (9th ed); will not be discussed in class.

III. Pacemakers
A. What is pacemaker activity? Cell membrane gradually depolarizes without any external stimulus. See Sadava
fig. 50.5
1. No stable RMP -- have pacemaker potential instead.
2. Cell gradually depolarizes, reaches threshold, and fires an AP.
B. Where are the pacemaker cells ?
1. All cardiac muscle and some smooth muscle have cells with pacemaker activity.

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

2. Only some cells in each muscle, not every single cell, have pacemaker activity.
Not all individual cardiac muscle cells or all individual smooth muscle cells (in single unit muscle) have
pacemaker activity. Only a few specialized cells act as pacemakers.
C. Role of pacemaker cells: Enables cardiac muscle and some smooth muscle to contract without nerve input,
because these muscles contain pacemaker cells. The pacemaker cells depolarize (and usually fire APs) simultaneously,
and this stimulates the other cells, the contractile cells (that do not have pacemaker potentials), to contract.
D. How do Pacemakers work?
1. Depolarization caused by opening/closing of ion channels. Pacemaker potential (spontaneous
depolarization) results because of opening/closing of ion channels. To start, more Na+ goes in and/or less
K+ leaks out. (Authorities differ in the details.)
2. It's a Cycle: When depolarization reaches threshold, cell fires an AP. Membrane then hyperpolarizes,
and depolarization starts again.
3. How do hormones and/or neurotransmitters affect pacemakers? Signal molecules can effect
opening/closing of channels and thereby alter time required to reach threshold.
4. Channels involved -- different from usual ones needed to generate RMP, AP etc. If you are curious
about the details, see physiology texts or Sadava fig. 50.5 (10th ed only)
Question: What triggers opening of the channels responsible for the pacemaker potential? Are the
channels ligand gated? Voltage gated? Mechanically gated?

IV. Smooth Muscle -- How does it Contract?

A. Important properties -- Can integrate multiple signals and maintain "tone" (state of tension/contraction) over
wide range of length with economical use of ATP.
B. Important Features of Structure
1. Arrangement of actin/myosin bundles -- see handout 22A or this picture.
2. Intermediate filaments -- connect dense bodies & help hold bundles in place. (Dense body = same
function as Z line in skeletal muscle.)
3. Two Types (reminder)
a. Single Unit smooth muscle -- the cells are connected by gap junctions and contract as a
unit.
b. Multi unit smooth muscle -- the cells are not coupled electrically; cells are stimulated and
contract individually.
4. Structure of nerve/muscle synapse -- not same as in skeletal muscle. Compare handouts 22A
(nerve/smooth muscle) and 20A (nerve/nerve --similar to nerve/skel. muscle).
C. How Ca++ Triggers Contraction.
1. Requires Calmodulin.
a. What is Calmodulin? It's the major Ca++ binding protein.
file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

b. Role of Calmodulin: Many effects of Ca++ are modulated by calmodulin. Ca++ binds
calmodulin, and then complex binds to target proteins, activating (or inhibiting) target
proteins. (See Becker 14-14.)
c. For role of calmodulin in smooth muscle contraction, see Becker fig. 16-24, or Sadava
48.9 & handout 22A.
2. Activates myosin. See 22A
a. Calmodulin-Ca++ complex forms
b. Calmodulin--Ca++ complex binds to and activates a kinase (MLCK)
c. Kinase phosphorylates and activates myosin (so it can bind actin).
d. How do 2nd messengers influence this? See 18B.
IP3 increases cytosolic Ca++, causing contraction.
The cAMP pathway (through PKA) phosphorylates myosin kinase (MLCK).
Phosphorylation of MLCK inhibits binding of MLCK to Calmodulin, causing
relaxation.
3. Bridge Cycle. Myosin binds actin, and bridge cycle follows; details not completely known.
4. Where Ca++ comes from:
a. Some Ca++ comes from outside of cell, through Ca++ channels in the plasma membrane.
b. Some Ca++ is released by the ER.
c. Proportion of Ca++ from outside and proportion from ER varies. Usually, most is from
the outside.
Note (FYI): Voltage gated Ca++ channels, not voltage gated Na+ channels, are responsible for
the rise in the spike of the AP in smooth muscle. Therefore Ca++ enters during the spike.
Try Problem 9-6, 9-13 & 9-14.

V. Skeletal Muscle -- How does it Contract?-- see animations listed at start of lecture, and handouts 22A &
B.
A. Overview of skeletal muscle structure & role of actin & myosin -- see handout 22A or Sadava fig. 48.1 & 2
or Becker Ch. 16, figures 16-10 to 16-15 for structure; fig. 16-16 for sliding model.
B. Overview of Bridge Cycle
1. Normal Cycle
a. Before cycle starts -- actin & myosin not connected -- myosin 'cocked' and ready to go
(stage B on handout)
b Role of Ca++ -- to uncover actin (not to activate myosin) -- allow step 1 on handout.
c. Uncovering actin starts the cycle (steps 1 & 2): allows myosin to contact actin (step 1) and

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

push the actin over one notch (step 2).

d. Role of ATP -- needed to separate actin and myosin (step 3) and prepare them for the next
round of bridge cycle by 'cocking' the myosin (step 4).
2. Where cycle stops
a. If no Ca++ (but normal ATP) -- Actin unconnected to myosin, but myosin 'cocked' and ready to go
-- stage B
b. If low ATP (but normal or high Ca++) -- Actin stuck to myosin -- rigor mortis -- stage D
C. Details of Bridge Cycle (FYI) -- -- steps (1 to 4) & states (A to E) match those on handout 22B. See also
Becker 16-18; Sadava fig 48.6 -- this includes role of Ca++ as well as ATP.
Cycle can start anywhere, but description below assumes you start with state B on handout and carry out step 1
first. (This is the normal start point when Ca++ triggers contraction.)
1. Myosin binds to actin -- converting state B state C (P i released; ADP remains bound to myosin)
2. Power stroke -- myosin, actin slide relative to one another. Myosin straightens up, pushing actin to left - converting state C state D. (ADP released) .
3. Myosin detaches from actin -- converting state D state E = state A. (Requires binding of ATP).
4. High energy or 'cocked' form of myosin formed -- Converting state A/E to state B. (Requires splitting of
ATP.)
5. Continue with step 1. Note ATP must continue to be split to maintain cross bridges and therefore
tension in fiber.
6. How bridge cycle is blocked/regulated
a. In absence of Ca++, bridge cycle is blocked at step 1 above. See below.
b. In absence of ATP (& presence of Ca++), cycle blocked at step 3 (rigor mortis).
7. Summary of how ATP is used to power sliding of thick and thin filaments in striated muscle.
a. Pi released at step 1.
b. ADP released at step 2 -- during or after power stroke.
c. ATP bound at step 3.
c. ATP split (hydrolyzed) at step 4 -- ADP & Pi remain bound.
Try problem 9-1, 9-11, and 9-12. Consult the bridge cycle handout if needed.
D. Overall Role of ATP & ATPase in bridge cycle
1. ATP must be split to run bridge cycle in all types of muscle. In smooth muscle, ATP is needed, in
addition, to activate myosin using myosin kinase (MLCK).
2. Myosin (not actin) has the ATPase activity. The catalytic site that splits ATP during the bridge cycle is
in the myosin head (myosin is the 'motor' molecule).

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

3. Speed of cycle. The bridge cycle is similar in smooth and skeletal muscle, but speed of cycle is much
slower in smooth muscle. In smooth muscle, cross bridges stay intact longer.
E. Role of Ca++ & protein complex (troponin and tropomyosin) See Sadava fig 48.3 or Becker 16-19.
1. Overall
a. Low Ca++ -- protein complex covers myosin binding sites on actin. (Step 1 on handout is
blocked.).
b. High Ca++ -- Ca++ binding causes protein complex to change conformation, uncovering
the myosin binding sites. Step 1 can proceed.
2. Protein complex details (FYI)
a. Protein Complex = Tropomyosin & troponin.
b. Location -- Tropomyosin and troponin are part of the thin filaments (bound to F-actin).
One molecule of tropomyosin covers several molecules of G-actin.
c. Tropomyosin role -- blocks myosin binding sites on actin
d. Troponin role -- Ca++ binds to troponin (not tropomyosin)
e. Effect of Ca++ binding -- binding to troponin movement of tropomyosin, exposing
binding sites on actin , so myosin can bind and bridge cycle can start
F. How does motor neuron trigger contraction in skeletal muscle? See Becker fig. 16-21 or Sadava 48.5
1. Presynaptic side: AP comes down motor neuron releases transmitter (AcCh)
2. Postsynaptic side -- events at membrane/motor endplate:
a. AcCh binds to nicotinic receptors on motor endplate (See texts for detailed structure of
endplate & synapse)
b. Depolarization of muscle membrane = EPP (end plate potential)
c. One AP in neuron One EPP = sufficient depolarization to trigger AP in membrane
of muscle fiber (One EPSP is not sufficient to trigger an AP in postsynaptic neuron.)
d. AP in muscle fiber triggers release of Ca++ contraction of muscle.
3. T tubules & SR -- Where does the Ca++ come from?
a. AP in muscle plasma membrane (sarcolemma) spreads to T tubules. (T tubule =
extension of membrane deep into the muscle fiber.)
b. AP in T tubule membrane Ca++ release from SR. Changes in membrane potential in
T tubule change in shape of protein in T tubule membrane opening of channels in SR
(SR = sarcoplasmic reticulum = ER of muscle cell) release of stored Ca++
(Coupling is probably mechanical between a voltage sensitive protein in the T tubule membrane and the

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

channel in the SR membrane. The coupling system is similar, but not exactly the same, in smooth &
cardiac muscle. Details of Excitation-Contraction coupling in muscle are in Lecture 22 of '05 if you are
interested.)
Try problems 9-2 & 9-4. Consult the bridge cycle handout if needed.
G. Twitches and Contractions
1. What's a twitch = 1 contraction = response to one EPP; measured by force exerted by muscle fiber when
it contracts.
2. Twitches in skeletal muscle are summed. See Sadava fig. 48.10
a. Twitch lasts longer than muscle membrane AP.
b. Second AP can trigger twitch before first is over more contraction (shortening)
c. Tetanus: Multiple AP's can fully contracted muscle that stays contracted = tetanus
(requires continual splitting of ATP to maintain contraction).
3. Twitches/contractions in cardiac muscle are not summed
a. Special features of AP in cardiac muscle membrane
(1). AP lasts much longer (as long as contraction). See Sadava fig. 50.8 (50.7).
(2). Cause of long AP. Prolonged AP (long depolarized phase) is due to delay in
opening of slow voltage gated K + gates and to opening of Ca++ channels. See
handout or Sadava fig. 50.8 (50.7).
(3). Result of long AP -- Extended refractory period prevents heart muscle
tentany. Each contraction ends before next AP arrives. Next contraction cannot
occur until previous contraction is over. (Compare to skeletal muscle.)
b. Role of Pacemakers.
(1). Trigger for contraction is signal from pacemaker cells of heart, not from AP
of nerve.
(2). Contractile cells do not have pacemaker activity. Only selected cells -- those
in nodes -- have pacemaker activity. See Sadava fig. 50.7
(3). What controls pace of heart beat? Autonomic neurons release transmitters
that slow or speed up pace set by pacemakers. See Sadava fig. 50.5
c. Cells are coupled electrically (gap junctions at intercalated disks)
4. What accounts for differences in function between the two types of cardiac cells? Differences in AP
between skeletal and cardiac muscle? Have different channels. If you need more details, consult physio or
neuro texts to see how differences in electrical properties correlate with differences in channels, ion flows,
etc.
5. Speed. (FYI!) Speed of twitch depends on multiple factors. The following information is included FYI
only for those interested in exercise physiology. There are two main types of fibers, fast twitch and slow
twitch. (See tables below for more details if you are interested.)

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

a. Fast/slow vs glycolytic/oxidative: Usually fast twitch fibers are glycolytic; contract quickly
but fatigue easily; Slow twitch fibers are oxidative -- contract slowly but fatigue more slowly.
Some muscle fibers are fast but oxidative.
b. Effect of Exercise:
(1). Exercise changes enzyme content and therefore glycolytic/oxidative differences, but
not slow vs. fast or # fibers. (Does change fiber size.) Slow and fast are innervated
differently, and that can't be changed.
(2). Exercise increases mostly size of fibers, not number. A limited number of muscle stem
cells exist, so minor repairs are possible. Major repairs and big increases in fiber number are
not possible.

VI. How does Contraction Occur?

Some important differences to keep track of are summarized here for reference; details about striated and
smooth muscle contraction are above.
a. What protein binds Ca++? Calmodulin or different (troponin/tropomyosin) complex?
b. What protein is altered to allow contraction -- actin or myosin? What is affected,
thick or thin filaments?
c. When actin or myosin is altered, what is nature of change? Change in conformation
&/or in state of phosphorylation?
d. Where does the Ca++ come from? Primarily extracellular or ER?
e. Is ATP needed to maintain contraction?
At this point, if you haven't done it yet, it helps to start making a table that summarizes all the significant
similarities and differences between the 3 types of muscle. Fill it in as you go -- add to it as you find out more about
the structure and function of the different types.
The remainder of the material is included FYI in case you are interested, or studying for MCAT or GRE.

VII. Additional Interesting (Optional) Material

A. Details of Types of skeletal muscle fibers and contractions -- See Sadava fig. 48.11. If you are interested, see
Sadava, section 48.2.
1. Muscle can be fast twitch or slow

Fast Twitch

Slow Twitch

ATPase of Myosin

Higher

Lower

Speed of Bridge Cycle

Faster

Slower

Reach max. tension (after EPP)

Rel. quickly

Rel. slowly

Size/ max. possible tension

Usually larger

Usually smaller

Overall Properties of Muscle

"flash in the pan"

"slow but steady"

Used for

quicker response, bursts of

activity (sprinters)

slower response, sustained activity

(long distance runners)

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

2. Muscle can be oxidative or glycolytic

Glycolytic

Oxidative

Color

paler ("white meat")

Red color due to myoglobin to store oxygen ("red meat")

# of capillaries to deliver
Rel. low
oxygen

Relatively high

# of mitochondria for
oxidative metabolism

Rel. low

Relatively high

Need for oxygen

Low

High. Need more oxygen but less glucose -- "Oxygen dependent"

but energy metabolism is more efficient

Ease of Fatigue

Rel. quickly

relatively slowly -- Does not accumulate lactic acid

Glycolytic enzymes

Higher

Lower

VIII. Heart Muscle Contraction -- more details.

A. Two Types of cardiac muscle cells
1. Contractile cells
a. Bridge cycle etc. much like skeletal.
b. FYI: Similar to oxidative/slow twitch skeletal (see above) -- low fatigue rate but very
oxygen dependent.
2. Pacemaker cells -- see Sadava fig. 50.5 and details above.
See Problems 11-1 & 11-2.
B. Structure of Heart. See texts or web for pictures if you are curious. In real pictures and diagrams, the 2 halves
of heart are joined, not separate, unlike diagram on handout 18A. Note that all pictures of heart show person facing
you, so 'right' 1/2 of heart is on left of picture.
C. Position, function of pacemaker cells (nodes), bundle of His, Purkinje fibers -- see Sadava fig. 50.7
1. All these cells have pacemaker activity -- make up the conduction system -- carry the AP to all parts of
the heart. Note these cells are muscle, not nerve.
2. SA node usually in charge. SA node has the fastest firing rhythm -- normally controls heart beat. Fires
first.
3. Role of AP in SA node. Causes atria to contract, pushing blood into ventricles. Causes AV node to fire
after a short delay
4. AP in AV node spreads to bundle of His and Purkinje fibers
5. Bundle of His etc. causes ventricles to contract, from bottom up, pushing blood out top of heart.
D. Review of Overall view of circulation-- (See handout 18A and Sadava, chapter 50)
1. There are 2 loops of circulation -- to lungs (pulmonary) and to body (systemic) -- see picture on bottom
of handout and Sadava p. 1030 (1050).

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]

Lecture 22

2. How reach tissues? Different blood vessels go in parallel to various parts of body. See handout 18A.
3. Arteries go away from the heart; don't necessarily carry oxygenated blood
4. Structure of blood vessels: Arteries and veins, arterioles and venules are surrounded by smooth muscle;
capillaries are not. Structures are shown in Sadava figs. 50.13 & 50.14.
Note: Gas exchange was discussed briefly in lecture 3 (see the section on the anion exchanger.) A more detailed
discussion of Gas Exchange is in Lecture 23 of '05 and Sadava Chapter 49. The details of this topic (and sections B &
C above) will not be covered in lecture and you are not responsible for them. A link is included if you are curious or
studying for MCATs.

file:///C|/Users/dbm2/Documents/COURSES/C2006/current-lectures14/lect22.14.html[4/20/2014 11:26:28 AM]