CARDIOVASCULAR PHYSIOLOGY

A. Examining the Effect of Temperature on Heart Rate

a. Introduction
Humans are homeothermic, which means that the human body
maintains an internal body temperature within the 35.8-38.2°C range
even though the external temperature is changing. When the external
temperature is elevated, the hypothalamus is signalled to activate
heat-releasing mechanisms, such as sweating and vasolidation, to
maintain the body’s internal temperature. During extreme external
temperature conditions, the body might not be able to maintain
homeostatis and either hyperthermia (elevated body temperature) or
hypothermia (low body temperature) could result. In contrast, the
frog is poikilothermic animal. Its internal body temperature changes
depending on the temperature of its external environment because it
lacks internal homestatic regulatory mechanisms.

Ringer’s solution consist of essential electrolytes (chloride, sodium,

potassium, calcium, and magnesium) in a physiological solution and is
required to keep the isolated, intact heart viable. The elecctrolyts
provide the necessary environment for the frog’s heart so that
spontaneous cardiac action potentials can occur.

b. Equipment used
 Oscilloscope display : to display the contractile activity from
the frog heart
 Electrical stimulator : to apply electrical shocks to the frog
heart
 Electrode holder : locks electordes in place for stimulation
c. Pre-lab quiz
 Organisms that usually maintain the same internal body
temperature in spite of environmental temperature change =
homeothermic
 The general name for the process that maintains the internal
body temperature in human = homeostatis
 The electrolytes in a Ringer’s solution are required to = provide
for autorhythmicity
 An internal body temperature that is above the normal range is
called = hyperthermic
 d. Experiment
 What effect will decreasing the temperature of the Ringer’s
solution have on the heart rate of the frog? = decrease in heart
rate
 What effect will increasing the temperature of the Ringer’s
solution have on the heart rate of the frog? = increase in heart
rate

Solution Heart rate

23°C Ringer’s 61
5°C Ringer’s 51
32°C Ringer’s 71

e. Post-lab quiz
 In the 5°C Ringer’s solution, the frog heart = beat slower than
baseline
 In the 32°C Ringer’s solution, the frog heart = beat faster than
baseline
 If the human heart were experiencing hypothermia, what will be
the effect on heart rate? = a decrease in heart rate
 Without the Ringer’s solution, what would not occur? =
spontaneous cardiac action potentials would not occur

B. Examining the Effect of Chemical Modifiers on Heart Rate

a. Introduction
Epinephrine in the body are adrenergic (elating to or denoting nerve
cells in which epinephrine (adrenaline), norepinephrine (noradrenaline),
or a similar substance acts as a neurotransmitter). If the modifier
works in the same fashion as the neutrotransmitter (acetylcholine or
norepinephrine), it is an agonist.
b. Equipment used
 Oscilloscope display
 Apparatus : to sustain an insolated intact frog heart (includes
23°C Ringer’s solution)
 Pilocarpine
 Atropine
  Epinephrine
 Digitalis
 Frog heart
c. Pre-lab quiz
 What did the parasympathetic nervous system releases to
affect heart rate? = acetylcholine
 A cholinergic drug that worked the same as acetylcholine would
= be an agonist and decrease heart rate
 Norepinephrine affects the heart rate by = increasing the rate
of depolarization and increasing the frequency of action
potentials
 Which receptor bind norepinephrine and epinephrine? = β-1
adrenergic
d. Experiment
 Pilocarpine will decrease the heart rate
 Atropine will increase the heart rate
 Epinephrine increases the heart rate and mimics the
sympathetic nervous system
 Individuals with weakened hearts need to allow maximum time
for venous return and increased stroke volume and would
therefore most likely benefit from increased force of
contraction and increased heart rate

Solution Heart rate

- 60
Epinephrine 80
Pilocarpine 45
Atropine 70
Digitalis 41

e. Post-lab quiz
 Pilocarpine decreased the heart rate. Typical of cholinergic
agonists, it = decreased the frequency of action potentials
 The effect of atropine was to = mimic the sympathetic nervous
system
  The modifiers tested that decrease heart rate were = digitalis
and pilocarpine
 To increase heart rate, the best choice would be = epinephrine
and atropine

f. Review
 Describe the effect that pilocarpine had on the heart and why
it had this effect = Pilocarpine decreased the heart rate
because it is an acetylcholine agonist. It decreased the
frequency of action potentials. Pilocarpine stimulates vagal
endings whatever their function and has in consequence a
negative chronotrope and a negative inotrope effect. Atropine
paralyses vagal endings and hence entirely antagonizes
the heart actions of pilocarpine
 Does atropine inhibit or enchance the effects of acetylcholine?
= Cholingeric and adrenergic modifiers (including
atropine) inhibit, mimic or enchance the action
of acetylcholine in the body. Atropine is acholingeric antagonist
that block the acetylcholine receptor increasing the heart rate.

C. Examining the Effect of Chemical Modifiers on Heart Rate

a. Introduction
In cardiac muscle cells, action potentials are caused by changes in
permeability to ions due to the opening and closing of ion channels. The
permeability changes that occur for the cardiac muscle cell involve
potassium, sodium, and calcium ions. The concentration of potassium is
greater inside the cardiac muscle cell than outside the cell. Sodium
and calcium are present in larger quantities outside the cell than inside
the cell.

The resting cell membrane favors the movement of potassium more

than sodium or calcium. Therefore, the resting membrane potential of
cardiac cells is determined mainly by the ratio of extracellular and
intracellular concentrations of potassium.
 Phase of cardiac action
potential
Phase 0 (rapid depolarization)
Phase 1 (small repolarization)
Phase 2 (plateau)
Phase 3 (repolarization)
Phase 4 (resting potential)
Ion movement
Sodium moves in
Sodium movement decreases
Potassium movement out
decreases, calcium moves in
Potassium moves out, calcium
movement decreases
Potassium moves out, little
sodium or calcium moves in

Calcium channel blockers are used to treat high blood pressure and
abnormal heart rates. They block the movement of calcium through its
channels throughout all phases of the cardiac action potentials.
Consequently, because less calcium gets through, both the rate of
depolarization and the force of the contraction are reduced.
Modifiers that affect heart rate are chronotropic, and modifiers that
affect the force of contraction are inotropic. Modifiers that lower
heart rate are negative chronotropic, and modifiers that increase
heart rate are positive chronotropic. Therefore, negative inotropic
drugs decrease the force of contraction of the heart and positive
inotropic drugs increase the force of contraction of the heart.

b. Pre-lab quiz
 Which organelle in the cardiac muscle that stores calcium? =
sarcoplasmic reticulum
 Verapamil is a calcium-channel blocker. Its effects could be
describe as = negative chronotropic and negative inotropic
 When the cardiac muscle is resting, where is most of the potassium
found? = in the cytosol
 Resting cardiac muscle cells are most permeable to = potassium
c. Experiment
 Because calcium-channel blockers are negative chronotropic and
negative inotropic, what effect do you think increasing the
 concentration of the of calcium will have on heart rate? =
positive chronotropic, positive inotropic
 Excess potassium outside of the cardiac cell decreases the
resting potential of the plasma membrane, thus decreasing the
force of contraction. What effect it will initially have on heart
rate? = decrease heart rate
 Where in the cardiac muscle cell is most of the sodium normally
found? = outside of the cell

Solution Heart rate

- 61
Calcium 71
Sodium -34
Potassium -28

d. Post-lab quiz
 The addition of most of the ions resulted in = an erratic heart
rate
 The effect of potassium on the heart is = negative
chronotropic, negative inotropic
 The ion that had the most pronounced effect on heart rate was
= potassium
 Ectopic pacemakers can be caused by excessive leakage of
potassium into cardiac cells, resulting in pacemakers appearing
in abnormal locations in the heart muscle. This hyperkalemia
(excess potassium) decreases the resting potential of the
cardiac muscle cell. What effect would it have on the force of
contraction? = decrease, negative inotropic
e. Review
 Describe the effect that increasing the calcium ions had on the
heart on this activity = The effect of increasing the calcium
ions was positive chronotropic and positive inotropic. It caused
the heart rate to increase from 61 bpm to 71 bpm.
SKELETAL MUSCLE PHYSIOLOGY

Skeletal muscles characteristically span two joints and attached to the skeleton
via tendons, which attached to the periosteum of a bone. Skeletal muscles are
composed of hundreds to thousands of individual cells called muscle fibers,
which produce muscle tension (also referred to muscle force). Skeletal muscle
are remarkable machines. They provide us with the manual dexterity to create
magnificent works of art and can generate the brute force needed.

When a skeletal muscle is isolated from an experimental animal and mounted on

a force transducer, you can generate muscle contractions with controlled
electrical stimulation. Importantly, the contractions of this isolated muscle are
known to mimic those of working muscles in the body. That is, in vitro
experiments reproduce in vivo functions. Therefore, the activities you perform
in this exercise will give you valuable insight into skeletal muscle physiology.

A. The Muscle Twitch and the Latent Period

a. Introduction
A motor unit consists of a motor neuron and all of the muscle fibers it
innervates. The motor neuron and a muscle fiber intersect at the
neuromuscular junction. Specifically, the neuromuscular junction is the
location where the axon terminal of the neuron meets a specialized
region of the muscle fiber’s plasma membrane. This specialized region
is called the motor end plate.

The events that occur at the neuromuscular junction lead to the end-
plate potential. An action potential in a motor neuron triggers the
release of acetylcholine from its terminal. Acetylcholine then diffuses
onto the muscle fiber’s plasma membrane (sarcolemma) and binds to
receptors in the motor end plate, initiating a change in ion
permeability that results in a graded depolarization of the muscle
plasma membrane (the end-plate potential). The end-plate potential
triggers a series of events that results in the contraction of a muscle
cell. This entrie process is called excitation-contraction coupling.
The pulses used in this experiment will be administered by an
electrical stimulator that can be set for the precise voltage,
frequency, and duration of shock desired. When applied to a muscle
that has been surgically removed from an animal, a single electrical
stimulus will result in a muscle twitch, the mechanical response to a
single action potential. A muscle twitch has three phases:

1. The latent period: the period of time that elapses between the
generation of an action potential in a muscle cell and the start of
muscle contraction. Chemical changes (including the release of
calcium from the sarcoplasmic reticulum) occur intracellularly in
preparation for contraction.
2. The contraction phase: starts at the end of the latent period and
ends when muscle tension peaks
3. The relaxation phase: the period of time from peak tension until
the end of the muscle contraction
b. Equipment used
 Intact, viable skeletal muscle dissected off the leg of a frog
 Electrical stimulator: delivers the desired amount and duration
of stimulating voltage to the muscle via electrodes resting on
the muscle
 Mounting stand: includes a force transducer to measure the
amount of force or tension developed by the muscle
 Oscilloscope: displays the stimulated muscle twitch and the
amount of active, passive, and total force developed by the
muscle
c. Pre-lab quiz
 A twitch is = one contractile response to a single action
potential
d. Experiment
 Will changes to the stimulus voltage alter the duration of the
latent period? = No, changing the stimulus voltage will not
change the latent period
 What occurs during the latent period of the isometric
contractios? = All the steps of excitation-contraction coupling
occur

Voltage Length Active Passive Total Latent

force force force period
0.0 75 0.0 0.0 0.0 -
3.0 74 1.04 0.0 1.04 -
4.0 75 1.32 0.0 1.32 -
4.0 75 1.32 0.0 1.32 2.80
6.0 75 1.65 0.0 1.65 2.80
10.0 75 1.82 0.0 1.82 2.80

e. Post-lab quiz
 An action potential in a motor neuron triggers the release of
which neurotransmitter? = acetycholine
  The graded depolarization in the skeletal muscle fiber that is
elicited in response to one action potential from the motor
neuron is called = an EPP (end-plate potential)

B. The Effect of Stimulus Voltage on Skeletal Muscle Contraction

a. Introduction
The threshold voltage is the smallest stimulus required to induce an
action potential in a muscle fiber’s plasma membrane. As the stimulus
voltage to a muscle is increased beyond the threshold voltage, the
amount of force produced by the whole muscle also increases. This
result occurs because, as more voltage is delivered to the whole
muscle, more muscle fibers are activated and thus, the total force
produced by the muscle increases. Maximal tension in the whole muscle
occurs when all the muscle fibers have been activated by a
sufficiently strong stimulus (maximal voltage). Stimulation with
voltages greater than the maximal voltage will not increase the force
of contraction.
b. Post-lab quiz
 Active tension (or force) in a skeletal muscle fiber results from =
activation of cross bridge cycling via increased intracellular calcium
levels
 What is the amount of stimulus required to successfully recruit all
the muscle fibers into developing active force called? = maximal
voltage
 Why was a maximal voltage observed in this experiment? = At the
maximal voltage, all the muscle fibers contained in this muscle are
depolarized and they all develop active force
c. Review
 Describe the effect of increasing stimulus voltage on isolated
skeletal muscle. Specifically, what happened to the muscle force
generated with = Increasing the stimulus voltage on isolated
skeletal muscle increases the amount of active force produced by
the muscle. This happens because more fibers and motorneurons
are activated and leads to an increase in muscle force

C. The Effect of Stimulus Frequency on Skeletal Muscle Contraction

a. Introduction
When a muscle first contracts, the force it is able to produce is less
than the force it is able to produce with subsequent stimulations ithin
a relatively short time span. Treppe is the progressive invrease in
force generated when a muscle is stimulated in succession, such that
muscle twitches follow one another closely, with each successive
twitch peaking slightly higher than the other one before. This step-
like increase in force is why treppe is also known as the staircase
effect. For the first few twitches, each successive twitch produces
slightly more force thant the previous twitch as long as the muscle is
allowed to fully relax between stimuli and the stimuli are delivered
relatively close together.