This
is a short review of the cardiac cycle (covered at the beginning of the
course)
Introduction
In the previous several
readings, we looked at smooth muscle structure and function. In this reading,
we will begin the process of looking at cardiac muscles.
But first ...
We had to zip through
smooth muscles quickly, so I thought it might be useful to list some of
the main features of smooth muscles by way of review:
Smooth muscles are:
Much smaller than skeletal
muscles.
Not striated (irregular
sarcomere arrangement).
Filaments are arranged
diagonally across the cell.
More actin per myosin
filament (10-15).
MH's are found along the
entire length of the myosin filament.
MH's on both sides of
middle have lines of heads that contract filaments in opposite directions.
Actin filaments contracted
in opposite directions have a slightly overlapped organization which allows
maximum contraction.
Much greater percent contraction
than skeletal muscles (80-90% vs 10-20%).
Approximate a sphere when
fully contracted.
Primary role is controlling
cross sectional area in lumens.
Shortening of long axis
reduces perimeter.
Widening of short axis
further reduces the area of the lumen.
For large lumen areas,
multiple layers of cells and a fibrous (non-expandable) layer of connective
tissue is required for complete closure (sphincters).
To control cross sectional
areas, in most cases, long axes are oriented circumferentially around the
lumen.
What is the exception?
Why?
Smooth muscle cell layers
with long axes arranged longitudinally provide transport capability.
Circumferential contraction
clamps onto a bolus, while longitudinal contraction reduces friction along
its path (peristalsis).
Connective tissue
Each skeletal muscle cell
is encased in a layer of connective tissue.
Aggregates of skeletal
muscles are encased in another layer (fascicles).
The overal skeletal muscle
is encased in an outer layer of connective tissue.
Provides strength and
protection but reduces capacity to contract.
Smooth muscle cells are
embedded in an amorphous layer of elastic connective tissue which provides
some of the same functionality.
Smooth muscle cells have
no or much reduced SR relative to skeletal muscles.
All or most of the Ca
for contraction must come from extracellular fluid.
The cells are very small
and speed/power are not hugely important, so this is not a big disadvantage.
Caveoli (not present in
all smooth muscle cells) appear to speed up response a bit.
Since all the the Ca has
to enter the cells as a cross membrane positive (Ca++) current, smooth
muscle cells have a different looking AP.
There is No sodium depolarization,
There is a Ca+K plateau
(or maybe just Ca if Ca channels suppress K channels),
K channels cause repolarization.
There are two types of
smooth muscle cells.
Multi unit
Cells must be made to
contract individually.
Cells can be made to contract
by hormones or autonomic nervous system.
Contractions due to autonomic
neurons us varicosities, not NMJs (the autonomic neurons are further away).
Skin hairs, iris, large
vessels in vascular system.
Only phasic contraction
(of relatively short duration, higher energy use).
Single unit
Activation of a single
cell can cause an entire layer of cells to contract.
Gap junctions provide
connection of cytosol between adjacent cells, so the current (or ion concentration
increase, or generator potential) can pass freely from cell to adjacent
cell.
Desmosomes provide structural
integrity of cell connections (spot welds) (not connexon; connexon is what
the gap junctions are made of).
Found all along the gastrointestinal
tract, in the uterus, and in small arteries and veins.
Activated by
autonomic nervous system,
hormones, blood gases
(CO2),
low pH,
stretching (ion channels
similar to those found in proprioceptors),
myogenic (= auto excitation
by pacemaker cells, specifically cells of cajal in this case).
Tonic and phasic contraction
Tonic single unit smooth
muscles can remain contracted for very long periods without fatigue and
without using lots of ATP.
Mechanisms still under
investigation
Latch theory was developed
25 years ago. It still appears (I found articles from articles from 2008,
2009) that some form of regulation of ADP release is an important component
of tonic contraction.
Recent theory - rapid
polymerization (rapid creation of actin cytoskeleton between dense bodies
at the membrane) may stabilize the cell in the contracted position.
Other traditional explanations
which may contribute to tonic contraction include
Low concentrations of
ATP-ase
Lower concentrations of
ATP in muscle cell.
How is contraction of
smooth muscles turned on?
Replacement of troponin/tropomyosin
mechanism with calmodulin mechanism.
Ca attaches at attachment
sites in this mechanism as well.
Local reflexes
Many reflexes in smooth
muscles do not loop through the CNS (they do in skeletal muscle reflexes).
Connections can be made
to induce or inhibit contractions in nearby smooth muscle cells to facilitate
an operation.
Movement of a bolus.
Examples:
Contraction at the back
of the bolus, relaxation in front of it.
Detrussor-internal sphincter
interaction during urination.
Voluntary control of smooth
muscles (exception to conventional wisdom)
Micturation reflex:
Stretched detrussor muscle
excites autonomic nerve that causes detrussor contraction and inhibits
autonomic nerve that causes contraction in sphincter.
Neurons under voluntary
control can interact with the neurons of the autonomic nervous system (this
is VERY unusual).
Neurons under voluntary
control are able to inhibit or excite autonomic neurons used to control
the reflex, allowing the reflex to be over ruled.
Voiding when detrussor
is not stretched.
Inhibiting voiding when
detrussor is stretched.
This is NOT the
result of the external voluntary sphincter (that's a backup mechanism).
This process is illustrated
in the figure at right.
Reflex
When bladder is full,
stretch receptors initiate a current in the sensory neuron.
This information goes
to the reflex arc and is passed to the brain.
The current from the afferent
neuron initiates a current to the detrusor muscle that starts contraction.
The current from the afferent
neuron inhibits the current to the internal smooth muscle sphincter, which
causes relaxation and voiding.
Voluntary control
The decision, in the brain,
that this is a bad time to void allows voluntary control of the reflex.
The current originating
in the brain inhibits the reflex current to the detrussor muscle, preventing
contraction.
The current originating
in the brain over rides the inhibition on the internal sphincter, allowing
it to remain contracted.
Now ... Let's Go to
Cardiac Muscle Cells
Functional
and Morphological Differences Between Skeletal, Smooth, and Cardiac Muscle
Cardiac muscle, as
its name implies, is only found in the heart. Cardiac muscle cells are
also called "myocardia" and a single cell is often referred to as a "myocyte".
Cardiac muscles share
properties with both skeletal and smooth muscle types.
Like smooth muscle, cardiac
muscle is not under the conscious control of the somatic (voluntary) nervous
system, but rather, cardiac muscle is regulated by the autonomic (involuntary)
nervous system (although it does have afferent innervation by the somatic
nervous system - i.e., you can feel pressure in the heart).
The structure of cardiac
muscle shares some of the properties of skeletal muscles and some of the
properties of smooth muscles, but it also differs from both in several
key ways. In this section we will step through some of these similarities
and differences.
Appearance
Cardiac muscle is striated
and is composed of sarcomeres similar to those of skeletal muscles.
Cell size is small compared
to skeletal muscle, being very close to that of smooth muscle (average
length is about 100-150 um). It's thickness is slightly more than that
of smooth muscle cells (25-30 um).
Cardiac muscle cells contain
more mitochondria than skeletal muscles, so the striations are not as organized
as they are in skeletal muscle.
The muscle also has a
greater degree of branching than found in skeletal muscle.
The branched myocytes
provide force generation along many axes. Once again, we see how morphology
provides clues to function.
In skeletal muscle, the
object is to provide maximum power along a single axis.
In smooth muscles, force
is secondary and lumen closure is paramount.
In myocardia, both power
and closure matter.
Cardiac output is proportional
to the power applied.
The mechanism by which
the power is actually applied to the blood, however, is a form of closure
(i.e., tension on the spheroid chamber).
Contraction along just
one axis would not work as well.
Like smooth muscle, cardiac
muscle is made up of cells with a single nucleus.
Gap Junctions and Organization
of Adjacent Cells:
Recall that single
unit smooth muscle cells had gap junctions that joined the cytosol
of adjacent cells.
This allowed a speedy
transmission of current from cell to cell.
The adjacent cells were
held together by protein spot welds to keep them from moving around.
Smooth muscle cells overlapped
along their long axes to form cell aggregates and the gap junctions were
located along the sides of the cells.
In myocardia, the cells
are also joined together, but they are butted up against each other at
their ends.
The junctions between
connected myocardia are called intercalated discs.
The ends of the cells
are held together by protein (desmosome) spot welds (just as in single
unit smooth muscles) and the gap junctions are located within the intercalated
disks.
Here is a photograph of
a histological section of cardiac muscle taken through a light microscope.
The blue arrow points to an intercalated disk.
Here we see a scanning
electron microscope image of a single cardiac myocyte (heart muscle cell),
which has been mechanically separated from the mass of the myocardium.
The points at which this
cell is in contact with others via the intercalated discs are indicated
by arrows.
The wispy strands of material
on the surface are fine collagen fibrils of the intercellular collagen
network that makes up the intercellular network of connective tissue that
holds cells together laterally.
The ridges on the surface
are the Z-lines of the sarcomeres (back to z-lines as in skeletal muscles).
Courtesy
Israel Institute of Technology
More on Gap Junctions
in Myocardia. As in single unit smooth muscles, myocardia have gap
junctions that allow the cytosol of adjacent cells to be directly connected.
The gap junctions allow
the electrical current that activates the myocardia to pass directly from
cell to cell, obviating the need for synaptic transmission between cells
(no muscles have synaptic synaptic connections with other muscle cells)
or direct innervation of each cell (which is not possible in myocardia).
The coordination of the
heartbeat and the transmission of the current from one cell to the next
is dependent on the integrity and proper functioning of the ID's and gap
junctions.
Notice that, in the heart,
a direct path of electrical conduction has been created reminiscent of
current conduction in a neuron.
This connecting of cardiac
cells together so that an electrical signal can pass freely across them
is known as a syncytium.
The heart is divided into
two functional syncytia, the atria and the ventricles, separated by the
A-V bundle.
Maintaining the integrity
of gap junctions is vital to cardiac function.
Notice the irregular surface
of the intercalated disks to maximize the surface area of the interface.
How does the irregular
surface increase strength?
Here we see a photo
of an actual ID. Notice the sarcomeres on either side.
Cardiac Muscle Action
Potential
Recall that, in skeletal
muscles, the AP was just like a neural AP: only sodium and potassium were
involved (just 1-2 ms long).
Depolarization only had
to last long enough to push the current along and through the skeletal
muscle cell.
To keep the skeletal muscle
contracted, the skeletal muscle cell had to depolarize and repolarize many
times.
The strength of the contraction
was based on the summation of the twitches.
Recall that, in smooth
muscle, much or all of the Ca required for muscle contraction had to be
imported from the extracellular fluid.
The resulting positive
Ca current across the cell membrane changed the shape of the AP.
Ca channels are "slow"
(100 ms for AP).
No VG Na channels.
Contraction continues
for as long as the extracellular Ca keeps the actin and myosin cross bridges
active in multi-unit and phasic single unit smooth muscle cells.
Contraction continues
indefinitely according to latch theory.
I said most types of myocardia
have this sort of AP (remember, there are various types of heart muscle
cells!).
Two types of myocytes
have distinctively different appearing AP's.
Here we see the different
myocyte types.
Each has its own signature
AP.
Fast VG Na channels do
not function in the SA node or in the AV node.
It's not clear whether
they are absent or just inactive.
Resting potential is hegher
than for other myocardia.
High resting potential
may prevent Na channel depolarization.
(the VG Na channels as
a group that we have seen previously are collectively referred to as "fast"
as compared to the ones we'll see Monday).
The absence of the steep
VG Na peaks are important to the functioning of both the SA node and AV
node cells (we'll see why next class).
In most myocardia
AP's, .
The AP takes about the
same amount of time as in smooth muscle cells.
Notice that the cross
membrane K current does not dominate until the Ca channels close.
Refractory period in myocardia
extends beyond contraction and and nearly to the end of relaxation of the
muscle cells.
In skeletal muscles,
we can have temporal summation because the action potential is so short.
The absolute and relative
refractory periods were over well before the muscle cell was completely
relaxed.
As a result, we could
have temporal summation and that helped us to regulate muscle force.
The MUCH longer action
potential in myocardia means that temperal summation either cannot occur
or becomes extremely unlikely.
We don't want temporal
summation in the heart.
Why?
Role of the Sarcoplasmic
Reticulum in Cardiac Muscles.
Recall that, in skeletal
muscle, calcium was not part of the AP but was essential in mechanical
contraction.
This was because all of
the Ca came from the sarcoplasmic reticulum (which was inside of the sarcolemma).
Recall that, in smooth
muscle, the SR was much reduced or entirely absent.
Calcium from the extracellullar
fluid was a part of the AP (because we had a cross membrane calcium current).
Extra-cellular and (if
present) intracellular Ca activated the actin fibers to initiate muscle
contraction.
In myocardia, the
role of the SR falls between that found in smooth and skeletal muscle cells.
The SR is less developed
than that of skeletal muscle but more developed than that of smooth muscle
cells.
The SR contributes Ca
to the contraction process, but to a lesser extent than that of skeletal
muscle SR.
Hence, Ca from extracellular
fluid is required for a strong muscle contraction to occur.
The heart muscle cells
need both extracellular Ca and Ca from the SR.
Myocardial T-Tubules.
Skeletal muscle cells
are huge. The need a transverse tubule system to get current to the vicinity
of the sarcoplasmic reticulum in order to activate dihydropyridine receptors.
Smooth muscle cells need
to bring in Ca from extracellular fluid in order to initiate contraction.
They are small.
Speed and precision of
contraction are not critical.
No T-tubule system is
needed.
Myocardia are nearly as
thin as smooth muscle cells but they do have a well developed t-tubule
system.
Predictability and uniformity
of performance are very important in the heart and a t-tubule system contributes
to this.
It transports both current
and
Ca to the cell interior.
Since Ca is a large ion,
the t-tubules have to be wider than those found in skeletal muscles.
Here is a drawing
that shows the myocardial t-tubule system. The tubules are 5 times wider
than those found in skeletal muscles to accommodate the large Ca ions in
the extracellular fluid that must reach the cell interior.
Here is an electron
micrograph of myocardia showing the t-tubules. T-tubules in myocardia also
occur along the Z-disks.
In skeletal muscle,
membrane depolarization is sensed by the dihydropyridine receptor, which
signals release of Ca from the SR through the ryanodine receptor.
The DHPr and Ryr in
skeletal muscles appear to be directly connected, so that the conformational
change of one results in the conformational change of the other when the
membrane has depolarized.
