Cardiopulmonary Physiology
Millersville University
Dr. Larry Reinking
Chapter 4 - Characteristics of Cardiac Muscle Cells.
This chapter deals with the properties of heart muscle cells and will serve as background
information for future laboratory and lecture sessions. In previous courses, you have learned
about the mechanical and electrical properties of skeletal muscle. We will review these concepts
and use them as a foundation for learning about heart muscle. As you will see, there are
similarities as well as vast differences between these two types of striated muscle.
General Terminology and Structure
The prefixes myo- and sarco- are frequently used when referring to striated muscle cells
and their organelles. Hence, we speak of the sarcoplasm (cytoplasm) or sarcoplasmic
reticulum (endoplasmic reticulum). Heart muscle is also called cardiac muscle or
myocardium. Skeletal muscle is a syncytium, that is, the individual cells are fused and form a
long, multinucleate fiber (called a myofiber). This arrangement of cells seems to enhance
communication and coordination within the muscle. Cardiac myofibers have distinct boundaries
between the cells called the intercalated discs. These cell boundaries are very permeable and
offer little resistance to cell-cell communication. Hence, cardiac muscle is a functional rather
than an anatomical syncytium. The histological appearance of cardiac muscle is also distinct
from skeletal muscle in that it is highly branched and has centrally located nuclei:
intercalated dis c
nucleus
cardiac muscle
skeletal muscle
Figure 4.1 Striated Muscle
Contraction of Striated Muscle
As seen above, skeletal muscle and cardiac muscle have a characteristic striated
appearance. This appearance is due to a regularly repeating pattern of contractile proteins within
the muscle cells. Each contractile unit, known as the sarcomere, is about 2 m in length and can
be depicted as follows:
actin
myosin
Z-line
= Ca2+
actin
cross -bridge
myos in
res ting
contracting
sarcomere
Figure 4.2 Sarcomere
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Contraction of striated muscle involves ‘cross-bridging’ between the protein filaments,
actin and myosin. Repeated cross-bridging causes these filaments to slide past one another and
results in muscle shortening (i.e., the Sliding Filament Theory). The trigger that promotes
cross-bridging is a sudden rise in intracellular calcium levels; at rest there is almost no free
calcium in the cytoplasm. Be aware that other regulatory proteins are involved in this process but
are not shown in the diagram. ATP, of course, is needed for muscle contraction and appears to
be involved in breaking cross-bridges and ‘re-energizing’ these broken cross-bridges.
Calcium and Muscle Contraction
In resting muscle, almost all intracellular calcium is unavailable because it is sequestered
in the sarcoplasmic reticulum. The following diagram illustrates the sarcoplasmic reticulum
and its relationship to contractile proteins; note the extensions from the cell membrane (T
tubules) that penetrate into the cell’s interior:
cell
membrane
T tubule
= Ca
2+
contractile
proteins
s arcoplasmic
reticulum





contractile
proteins
skeletal muscle
cardiac muscle
Figure 4.3 Calcium and the Sarcoplasmic Reticulm
During excitation of a skeletal muscle, neurotransmitter from a nerve signal will initiate
an action potential (defined below) that is propagated along the cell surface and down the T
tubule membrane. The T tubule action potential, in turn, will cause the sarcoplasmic reticulum
to release stored calcium; cross-bridges then form and the muscle contracts. Calcium pumps (i.e.,
active transport) re-sequester calcium and the muscle returns to the resting state. Skeletal muscle
is not affected by extracellular calcium.
In contrast, cardiac muscle has a complex calcium ‘circulation’ and is greatly affected by
external calcium concentrations. Note in the above diagram that the T tubules of cardiac cells are
large and enhance contact with extracellular calcium. The following steps are hypothesized for
cardiac muscle: Following arrival of the T tubule action potential, calcium enters from the
extracellular fluid . Most of the entering calcium triggers a large (heavy arrow) release of
stored calcium from the sarcoplasmic reticulum . This released calcium, plus a small portion of
the entering, extracellular calcium , promote cross-bridging and muscle contraction.
Following contraction, most of the calcium is ‘pumped’ back into the sarcoplasmic reticulum .
The remaining free calcium is ejected from the cell to the exterior by either a cell membrane
calcium pump  or a membrane carrier that exchanges external sodium for internal calcium .
Action of Cardiac Glycosides
Cardiac glycosides such as digitalis increase cardiac contractility. The major action of
these drugs is the inhibition of membrane sodium pumps (which pump Na out of the cell). The
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resulting accumulation of intracellular sodium inhibits the sodium-calcium exchanger ,
depicted in the above diagram. The ultimate result is more free intracellular calcium, more crossbridging and thus, more contraction.
Electrical Activity of Muscle Cells
Like other excitable cells, striated muscle has a resting electrical potential and propagates
signals via an action potential.
Resting Potential
At rest, muscle cells have an unequal distribution of positive and negative ions across the
membrane. This results is an electrical potential, called the resting potential that has a typical
value of -90 mV in striated muscle (an exception will be cardiac nodal tissue):
+
+ + ++ + + + + + + + +
-- - - - - - - - - - ++
- -+ + +
- - - - - - - - - - - - - - + + + + + + + + + +
+ + +
Distribution of charges in a
resting cardiac muscle cell.
The resulting res ting potential
has a value of -90 mV.
Figure 4.4
Resting Cardiac Cell
An increase in the resting potential (i.e., a more negative value such as -100 mV) is called
an hyperpolarization. The opposite, a decrease in the resting potential is a depolarization. A
repolarization is the return to the resting potential after the depolarization of an action potential.
In cells such as nerve and muscle, the resting potential ‘sets the stage’ for excitability,
that is, the initiation of an action potential. A cell that has lost the resting potential will no longer
be excitable while a hyperpolarized cell will be more difficult to stimulate. The basis of the
resting potential is a combination of factors that include the sodium-potassium pump (Na/KATPase), chemical and electrostatic forces and membrane permeabilities to a variety of ions (Na,
K, Ca, Cl, and nondiffusible anions). The ‘bottom line’, for our purposes is the following - The
major cause of the resting potential is the potassium gradient and the resting membrane’s
permeabilty to K+. Potassium ion concentration is high within cells (135 mM) and is low in the
extracellular fluid (4 mM, see p.4, chapter 2).
Extracellular Potassium and Cardiac Function
Excess potassium in the extracellular fluid causes the heart to become weak and flaccid.
The reduction of the potassium gradient induces a depolarization that, in turn, results in a weak
cardiac action potential (the magnitude of the cardiac action potential is related to the strength of
contraction). An elevation of serum potassium to only 8-12 mM is sufficient to induce abnormal
cardiac function and death. For this reason there is extreme clinical concern for patients with
renal failure; renal failure is accompanied by a rapid rise in serum potassium. During ‘bypass’
surgery, a common way to stop the heart is to simply pour a cold solution of potassium chloride
into the thoracic cavity. The heart immediately stops beating due to the combination of cold and
the loss of the potassium gradient.
Action Potential
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The action potential is a nondegradatory, self propagating wave of depolarization. In
skeletal muscle, the duration of an action potential is limited to several msec while a cardiac
action potential may last for hundreds of msec. Figure 4.5 depictions action potentials and the
associated ionic events for skeletal and cardiac muscle. Cardiac nodal tissue differs from either
of these patterns and will be examined later in this chapter.
Figure 4.5 Muscle Action Potentials
(heavy arrows = fast current; light arrow = slow current)
+30
K out
Na in Cl in Ca in K out
K out
+
-
+
+
resting po tential
+
resting po tential
membrane potential (mV)
Na in
skeletal
muscle
+
+
cardiac
muscle
4
0 1
2
3
4
-90
10 msec
400 ms ec
The skeletal muscle action potential has two basic phases. Upon achieving a threshold
stimulus (recall the all-or-none principle), sodium gates in the membrane open, sodium ions rush
in, the membrane rapidly depolarizes and 'overshoots' to about +30 mV. A rapid repolarization
+
follows that is due to closure of the Na gates and to outward moving potassium ions. As a
result, the membrane returns to the resting potential.
In contrast, the cardiac action potential takes much longer, has five phases (0-4), a variety
of ionic events and varies in characteristics from one region of the heart to another. Its nature
will also change depending on the type of stimulation: if threshold is achieved swiftly, a large,
rapidly rising action potential occurs but if the stimulus gradually reaches threshold, then a
slowly rising, small action potential results.
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Phase 0 (‘the upstroke’) is caused by an opening of the sodium gates and an entry of sodium
ions. These gates open fully with rapid stimulation or open only partially with a gradual
stimulus.
Phase 1 (‘early repolarization’) is caused by a brief outward movement of K+ and a simultaneous
inward movement of Cl-.
Phase 2 (‘the plateau’) is most notable since it creates a prolonged refractory period (time
during which a muscle cannot be re-excited). The plateau is maintained, primarily, by a slow
inward movement of calcium ions. In addition to contributing to the plateau, these entering
calcium ions interact with the contractile proteins to form cross-bridges.
Drugs Effects and the Plateau - Catecholamines (epinephrine and norepinephrine) increase the
slow, inward calcium current of phase 2. This action seems to be the primary mechanism for
increased cardiac contractility caused by epinephrine and norepinephrine (remember, more
internal Ca, more cross-bridging). Calcium channel blockers (e.g. verapamil, nifedipine,
dilitiazem) impede this slow, inward calcium current and, thus, decrease the strength of cardiac
contraction. Calcium channel blockers also have antiarrhythmic actions. One cause of heart
arrhythmia is a ‘reentry current’ that is, a flow of electrical current that inappropriately restimulates some area in the heart. Normal heart stimulation, of course, is initiated by the
pacemaker of the SA node. Reentry currents are likely to happen when isolated areas of the heart
remains depolarized for too long. Calcium channel blockers will decrease the time an area is
depolarized by shortening phase 2.
Phase 3 (‘repolarization’) is caused by a net outward movement of potassium ions which rapidly
returns the cardiac cell to its original resting potential. The repolarization that takes place during
this phase involves an interplay of several different types of potassium channels.
Phase 4 is the resting potential.
Types of Cardiac Muscle
Cardiac muscle can be categorized into different types of specialized cells. Basically,
there are cells that are specialized for contraction and those that are specialized for signal
conduction. Unlike many organs, the heart uses specialized muscle cells rather than neurons for
signal conduction.
Consult your lab handouts for diagrams and further information dealing with
cardiac cell types. This chapter also should be used in conjunction with the
transcript from the program “Electrical Anatomy of the Heart, Part I”.
1. Working Myocardium. These are the cells that make up the vast majority of the atrial
muscle, ventricular muscle and the intraventricular septum. They are highly striated and are
comprised mostly of contractile proteins and mitochondria (48% and 36%, by volume).
Consistent with the high density of mitochondria, these cells rely heavily on aerobic metabolism.
Within the atrial myocardial cells are dense granules that contain peptide hormones. When the
atria are stretched, these hormones are released and alter kidney and vascular function. Thus, the
heart is also an endocrine organ!
2. Conduction System. These cells are modified for rapid signal conduction and only exhibit
weak contractions. Correspondingly, the contractile proteins (20%) and mitochondria (10%) are
reduced in volume and cellular metabolism is mostly anaerobic. This type of cell is found in the
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bundle of His (also known as the AV bundle or common bundle), the bundle branches and the
Purkinje fibers.
3. Nodal Cells. The sinoatrial node (SA node) and atrioventricular node (AV node) are
comprised of small, pale cells that are only slightly striated. They are responsible for pacemaker
activity and regulate conduction from the atria to the ventricles. The electrical properties of these
cells differ from the other types of myocardium (see below).
4. Transitional Cells. These cells are the interface between the Purkinje fibers and the working
myocardium. Their histological appearance is intermediate between these two cell types. It has
been speculated that this type of cell may also form conductive tracts within the atria.
0
-70
slope
pacemaker
potential
membrane potential (mV)
Electrical Properties of Nodal Cells
Nodal tissue has a resting potential value that is less than other myocardium, has an
action potential upstroke of slow velocity, has no plateau and repolarizes slowly. Depicted,
below, is an action potential for the SA node:
Figure 5.6 Electrical Activity of Cardiac Nodal Tissue
SA
node
threshold
slope
100 ms ec
Note the slow upstroke which indicates the that fast sodium channels are not operating.
This is probably due to the ‘low’ initial resting potential since partial, slow depolarization is
known to inactivate fast sodium channels. In nodal tissue, the upstroke is due mostly to an
inward movement of calcium ions. Heart muscle is myogenic, that is the signal that initiates
contraction comes from within the muscle, not from a nerve impulse. The nervous input to the
heart will, however, modify the rate and strength of contraction. In the above diagram, note the
unstable resting potential which gradually depolarizes until it reaches threshold. This type of
resting potential is called a pacemaker potential. The gradual depolarization of the pacemaker
potential is due to a least three factors: 1) a slow decline in outward potassium movement, 2) a
slow inward calcium leak and, most importantly, 3) a slow inward current of sodium ions.
Control of heart rate, by the autonomic nervous system, is achieved primarily by increasing or
decreasing the slope of the pacemaker potential.
Sympathetic Stimulation (Norepinephrine)
Sympathetic stimulation (via cardiac nerves) of the SA node is mediated by -adrenergic
receptors and causes an increase in heart rate (tachycardia). This effect is brought about by an
increased inward movement of calcium and sodium ions, thus increasing the pacemaker potential
slope. -adrenergic antagonists (beta blockers) slow the heart by preventing binding to the adrenergic receptors.
Parasympathetic Stimulation (Acetylcholine)
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Vagal stimulation of the SA node causes a slowing of the heart rate (bradycardia).
Acetycholine’s effect is mediated by muscarinic type receptors which bring about a decrease in
the inward movement of sodium and calcium, thus decreasing the slope of the pacemaker
potential. Also, acetylcholine alters the heart rate by hyperpolarizing the resting potential. Since
the new starting point is farther away from threshold, it will take longer initiate an action
potential. This second effect is the result of an increased outward movement of potassium ions.
Calcium Channel Blockers
These agents slow heart rate by binding to calcium channels which will reduce the inward
leak of calcium.
Hyperkalemia (elevated serum K+)
The SA node especially sensitive to extracellular potassium. As noted previously, the
resting potential depends primarily on the transmembrane potassium gradient. Elevated serum
potassium causes a depolarization of the SA node and slow conduction velocity. Severe
hyperkalemia will bring about ‘SA block’.
Cardiac Glycosides
Digitalis and related compounds slow the heart rate by inhibiting the sodium pump
which, like hyperkalemia (above) depolarizes the cell thus depressing SA nodal function.
AV node
The action potential of the AV node looks similar to that of the SA node, however, the
resting potential is much more stable. The AV node has the slowest rate of electrical conduction
of all types of myocardium; this is due to the very small size of the AV nodal cells. Slow
conduction through this part of the heart allows completion of atrial pumping before the initiation
of ventricular contraction. Autonomic input to this node will slow (parasympathetic) or facilitate
(sympathetic) the rate of conduction.
Heart Rate and Action Potential Duration
As the heart rate increases the duration of time between beats becomes shorter.
Obviously, the prolonged action potential that is characteristic of most types of myocardium must
be shortened during high heart rates. During rapid heart rates, more calcium channels are open
and intracellular calcium levels rise. This rise in intracellular calcium stimulates an outward
movement of potassium via ‘calcium activated potassium channels’. This outward movement of
K+ rapidly repolarizes the myocardial cells, thus shortening the duration of the action potential.
More on Myocardial Resting Potentials
The preceding discussion may leave you with the impression that the SA node is the only
portion of the heart that is capable of autorhythmicity. In actuality, all types of myocardial cells
have unstable resting potentials and therefore are capable of initiating their own action potentials.
If a piece of working myocardium, for example, is placed in a beaker of warm Ringer’s solution
it will begin rhythmically contracting, although at a slow rate. The SA node has the most unstable
resting potential (steepest slope), the fastest rate of ‘firing’ and, therefore, is the pacemaker. If
the SA node is damaged some other region in the heart will become the center of pacemaker
activity and is called an ectopic pacemaker.
Summary Tables
This chapter contains a good deal of related information in different sections. The
following tables may help in ‘pulling together’ some of the concepts:
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Table 4.1 Properties of Skeletal Muscle vs. Cardiac Muscle
Difference
response
duration
stimulus
T-tubules
syncytium
substrates
Skeletal Muscle
stereotyped
few msec
nerve
small
true anatomical
lipid, CHO
Cardiac Muscle
variable
100+ msec
myogenic
large
functional
lipid, CHO, lactate
Table 4.2 Drug and Ion Effects on the Heart
Drug
cardiac glycosides
cardiac glycosides
catecholamines
catecholamines
acetylcholine
Effect
increase contractility
 heart rate / cond. vel.
increase contractility
increase heart rate
decrease heart rate
Mechanism of Action
Na pump  intracellular Ca
Na pump depolarizes SA & AV node
 inward Ca current during plateau
Na & Ca leak  slope of pacemaker pot.
Na & Ca leak  slope of pacemaker pot.
 outward K current  hyperpolarization
Ca channel blockers decreased contractility
 inward Ca current during plateau
Ca channel blockers antiarrhythmic
 Ca shortens plateau prevents reentry
Ca channel blockers slows heart rate
inward Ca leak  slope of pacemaker pot.
hyperkalemia
contractility, SA block loss of K gradient  depolarization
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