Animal Physiology
Review Questions
5 March 2001
Reminder note about units.
Ohm’s law relates current, voltage and resistance.
V = I*R; volts = amperes * ohms
typical units for neurobiology: millivolts = nanoamperes * megohms
I = G*V; amperes = siemens * volts; nanoamperes = microsiemens * millivolts
Charge = current * time; coulombs = amperes * sec
1. Ion concentrations for (marine) squid axon (mM):
internal
external
400
20
K+
Na+ 50
440
560
Cl- 52
Answers: Eion = (1/z)*58*log10([ion]o/[ion]i)
K: -75.5 mV; Na: + 54.8 mV; Cl: -59.9 mV
For a typical mammalian (terrestrial) cell:
internal
external
125
5
K+
+
12
120
Na
10
125
ClCalculate the Nernst potential for each ion in each cell.
Answers: K: -81.1 mV; Na: +58 mV; Cl: -63.6 mV
2. What is the dependence of axonal conduction velocity on axon radius for an unmyelinated axon? To
double the conduction velocity, but still keep the axon unmyelinated, how much does the cross sectional
area of that axon have to increase?
Action potential conduction velocity for an unmyelinated axon depends on the length constant, and
thus on the square root of the radius. To double conduction velocity, radius must be increased by a
factor of 4, and cross-sectional area must be increased by a factor of 16!
3. If a neuron’s membrane potential is –75 mV, the K conductance is 400 nS, and the K current measured is
5 nA, and the intracellular K concentration is 120 mM, what is the extracellular K concentration? If the
membrane potential is changed to –120 mV but conductance and ion concentrations don’t change, what is
the new current?
Iion = Gion * driving force = Gion * (Vmem - Vion); IK = 400 nS * (-75 mV – EK) = 5 nA; EK = -87.5
mV;
EK = 58 * log10([K]o/[K]i) = -87.5 mV; [K]o = 3.72 mM
Inew = G*(Vmem – EK) = 400 nS * (-120 - -87.5 mV) = 13 nA.
2
5.
Review Questions 3/5/2001
At the peak of the action potential, what is the sum of all ion currents? What is this sum just at the peak
of the afterhyperpolarization? What is the sign of the total ion current just after the peak of the
afterhyperpolarization? Is this inward, or outward?
At the peak of the action potential, dV/dt = 0, so the sum of all ion currents = 0. Same at the peak of the
afterhyperpolarization (AHP). Just after the peak of the AHP, the membrane potential is becoming
less negative (moving in the positive direction), so current is inward, or negative.
6. A glial cell has EK = –110 mV and ECl = – 65 mv. Its resting conductances for K and Cl are: 800 nS and
150 nS, respectively. What is the resting potential? What is the resting conductance? What is the resting
current carried by K? What is the resting current carried by Cl? If you place an electrode in the cell and
pass 4 nA of depolarizing current, what will be the asymptotic deflection in potential?
Resting potential is the weighted average of EK and ECl, weighted by the relative conductances.
Vrest = -110 mV * (800/950) + -65 mV * (150/950) = -102.9 mV
Ω
Conductance is 800 nS + 150 nS = 950 nS = 9.5 x 10-7S; resistance = 1/conductance = 1.05 MΩ
Current carried by an ion = driving force * conductance. IK = (-102.9mV – -110 mV) * 800 nS
= 5.68 x 10-9 A = 5.68 nA. ICl = (-102.9 mV - -65 mV) * 150 nS = - 5.68 x 10-9 A = - 5.68 nA.
Note ECl and EK are equal in magnitude, but opposite in sign.
V = I*R = 4 nA * 1.05 MΩ
Ω = 4.2 mV.
7. You record from a cell, and inject a small hyperpolarizing current of 100 pA. You observe that the
voltage reaches an asymptotic deflection of 7 mV, and that the time constant for the charging curve is 15
ms. What is the input resistance (resting resistance) of the cell? What is the cell capacitance? What is
the cell’s diameter, assuming it is spherical and the membrane has specific capacitance of 1 x 10-6 F/cm2.
V = I*R. R = 7 mV/0.1 nA = 70 MΩ
Ω.
t = R*C. C = t/R = 15 ms/70 MΩ
Ω = 0.214 nF = 214 pF
Total capacitance = specific cap. * area. area = 0.21 nF/(10-6 F/cm2) = 2.1 x 10-4 cm2
Area = 4*p*r2, so r = sqrt(area/(4*p)) = sqrt(2.1 x 10-4 cm2/(12.57)) = sqrt(1.67 x 10-5 cm2) = 4.1 x 10-3 cm
= 41 µm. Diameter = 80 µm. (This is a pretty large neuron!!!)
8. Describe the basic steps in fast chemical synaptic transmission. Make sure you can define or explain
these terms: reversal potential, synaptic cleft, neurotransmitter, postsynaptic potential
Action potential arrives at terminal; terminal depolarizes; voltage-sensitive calcium channels open;
calcium enters; vesicles containing neurotransmitter fuse with plasma membrane; transmitter diffuses
into and across synaptic cleft; transmitter binds to postsynaptic receptors; bound receptors open;
increased postsynaptic conductance to ions; current flows to take postsynaptic membrane closer to
reversal potential (Nernst potential if it’s a receptor/channel selective for a single ion, or the
equilibrium potential if multiple ions can permeate the channel) for the receptor; postsynaptic
membrane potential changes.
Reversal potential: the potential at which the sign of the synaptically activated current changes.
This is the Nernst potential if the channel is selective for a single ion, or some combination if the
channel can pass more than one ion.
Neurotransmitter: the substance released by the presynaptic terminal that causes the
postsynaptic response
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Review Questions 3/5/2001
Synaptic cleft: the small space between the presynaptic terminal and the postsynaptic
membrane
Postsynaptic potential: the change in membrane potential in the postsynaptic cell following
activation of a synapse.
9. A central pattern generator (CPG) is involved in insect ecdysis.
a. What are the key features of a CPG?
A CGP generates a pattern independent of sensory feedback.
b. How might a CPG contribute to ecdysis?
It contributes to the two types of rhythmic movements involved in ecdysis.
c. Describe the hormonal cascade that triggers the ecdysis motor pattern.
The ecdysteroid peak triggers a number of changes in the physiology of the Manduca, eventually
leading to a small release of ETH from the Inka cells of the epitracheal gland. The ETH acts on the
VM neurons, causing them to release EH. (ETH also acts directly on the motor system to induce preecdysis behavior.) Since EH acts back upon the Inka cells to stimulate more ETH release, this sets up a
positive feedback loop in which the VM neurons dump all of their EH into the blood and into the
central nervous system. EH increases cGMP levels in the 27/704 cell groups in the ganglia, thus
stimulating release of CCAP, which acts upon the motor circuit to induce the ecdysis motor pattern.
10. You are a Manduca larva getting ready to molt. How do you decide whether to become a pupa or go
through another larval instar?
If JH is present during the ecdysteroid peak, you will molt into the next larval instar. If there is a
small ecdysteroid peak in the absence of JH (commitment peak), then another ecdysteroid peak in
the presence of JH, you will become a pupa. If you experience a prolonged ecdysteroid peak
without any JH, you will develop into an adult.
11. You have 3 midterms and 2 papers due in a two-week period. The following week you and several of
your classmates all come down with a bad cold. What endocrine system is involved in this phenomenon?
What class of hormones mediates this effect and what organ releases them? What type of stressors
triggered the release of these hormones? From what general area of the brain did the information come to
activate this system? How did activation of this hormone system cause immune suppression?
The hypothalamic-pituitary-adrenal axis is responsible for the stress response, which is mediated by
glucocorticoids – steroid hormones – released by the adrenal gland. This response was triggered by
“processive” stressors, which involve some higher cognitive processing in the forebrain (as opposed to
“systemic” stressors, which send info directly from the brainstem to the hypothalamus). Prolonged
high levels of glucocorticoids inhibit the production of cytokines, a class of molecules involved in the
immune response. Chronic stress also reduces the levels of lymphocytes (T cells and B cells, the
workhorses of the immune system) in the bloodstream.
12. How is the mechanism of peptide hormone action similar to that of slow synaptic transmission?
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Review Questions 3/5/2001
Peptide hormones usually act by binding to a receptor that signals through a G-protein cascade.
Activation of the receptor causes the G protein to exchange GDP for GTP, which allows the G-alpha
subunit to interact with and activate an effector enzyme or ion channel.
13. Draw a diagram of negative feedback loops in an endocrine system. Include and indicate short- and longloop feedback pathways.
Hypothalamus
-
+
Anterior pituitary
-
+
Gland (e.g. gonad or
adrenal)
14. What are the 4 main classes of hormones discussed in class? Describe the main mechanism of action for
each. Over what approximate time scale does each act? Give an example from each class.
Class
Amines
Steroids
Peptides
Eicosanoids
Mechanism
Membrane receptor
Cytoplasmic receptor
influencing gene
expression
Membrane receptor
Membrane receptor
Time scale
Seconds - hours
30 mins. – days
Example
Adrenaline (epinephrine)
Testosterone
Minutes – hours
Minutes – hours
Insulin
Prostaglandins
(inflammation)
15. Describe the body’s response to a rise in blood glucose. To the extent we discussed in class, provide
cellular detail. Describe how this system exemplifies interacting feedback loops
See lecture notes at http://courses.washington.edu/zool485 “28 February Control of blood glucose”
16. What are gamma motor neurons? How do they play a role in voluntary movements?
Gamma motor neurons innervate intrafusal muscle fibers (also called spindle fibers) and cause them to
contract. They are important in voluntary movements because they are coactivated with alpha motor
neurons, which innervate extrafusal muscle fibers and cause the major force generation by the muscle.
Coactivation of gamma motor neurons removes the slack in the spindle fibers that would be caused by
contraction, allowing the stretch reflex to continue to work during and following the movement.
17. Describe the steps involved in generating a voluntary movement of the left leg. Be specific about what
events happen on which side of the body.
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Review Questions 3/5/2001
Regions of the motor portion of cerebral cortex in the right hemisphere become active. Some neuron
cell bodies in the primary motor cortex area of that hemisphere send their axons through the white
matter of the forebrain, through the cerebral peduncles (large ventral axon bundles visible at the level
of the midbrain) and pyramids of the medulla, crossing (decussating) to the left side of the body at the
caudalmost point of the medulla or rostralmost point of the spinal cord. These same axons descend the
spinal cord in the lateral region of white matter to the segment containing the motor neurons for the
muscle of interest, where they make excitatory synapses on the alpha and gamma motor neurons.
Action potentials descending these corticospinal tract axons excite motor neurons causing the muscle to
contract and the movement to be generated.
In addition, these axons send collaterals to the red nucleus, in the midbrain, which in turns sends axons
down the spinal cord in the rubrospinal tract. These axons are intermingled in the spinal cord with the
corticospinal tract axons and have largely the same function.
18. Describe how the stretch reflex works and what it accomplishes.
Intrafusal muscle (spindle) fibers are innervated by sensory neurons that are sensitive to stretch. When
a tendon or muscle is stretched, these sensory neurons are excited, sending action potentials through
the sensory nerve, which enters the spinal cord through the dorsal root. These fibers make synapses on
alpha motor neurons in the ventral horn and cause an increase in firing rate. This increased firing in
motor neurons, which innervate the extrafusal muscle fibers of that muscle, causes muscle contraction
to counteract the stretch.
19. What is the size principle for recruitment of motor neurons? What beneficial effect does it have for
movements?
A motor unit is a motor neuron and all of the muscle fibers it innervates. There is a range in the size of
motor units (the number of muscle fibers innervated by each motor neuron). The size of the motor unit
is also correlated with the size of the motor neuron and the amount of force generated by the motor
unit. The size principle refers to the tendency for small motor units to be recruited for small, low-force
movements, and larger motor units to be recruited later, if the movement requires greater force. This
recruitment order makes sense because small, low-force movements can have a higher degree of
regulation (finer force increments) than high-force movements.
20. How does smooth muscle contract? How does this differ from skeletal and cardiac muscle?
Smooth muscle through depolarization-induced rise in intracellular calcium, accompanied by release of
Ca from intracellular stores. This does not immediately cause contraction, however. Rather, several
enzymatic steps take place that ultimately allow myosin to slide against actin filaments. One of these
steps is binding of Ca to calmodulin, which activates myosin light chain kinase, which, when activated,
phosphorylates myosin, promoting interaction with actin. There are several additional pathways that
regulate Ca induced contraction in smooth muscle.
21. Describe how estrogens are thought to masculinize the young songbird brain.
In young male and female songbirds, the song nuclei begin essentially the same size. At some point, as
circulating hormones rise, testosterone is probably aromatized to estrogen in the brain, producing
relatively high local levels of estrogen in males. This allows neurons in, for example, nucleus HVc and
nucleus RA to survive. In females, neurons in these nuclei begin to die. They can be rescued by early
treatment with exogenous estrogen (or testosterone, but not by dihydrotestosterone, which cannot be
aromatized to estrogen).
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Review Questions 3/5/2001
22. Researchers have been trying for decades to produce a “male pill” that would block
spermatogenesis. One example of a drug that has been tested is a GnRH antagonist. This drug
blocks GnRH receptors and keeps them from “seeing” that GnRH is present.
a) Where (anatomically) would this compound act?
GnRH is released from the hypothalamus and acts in the pituitary. Thus, such an
antagonist would have to work in the pituitary.
b) In one sentence, describe how this compound would block spermatogenesis.
The compound would block the release of FSH by the pituitary, which is stimulated by
GnRH. FSH acts on the testes to stimulate spermatogenesis.
c) In clinical trials of this drug, men complained about some troublesome side effects. In one
sentence, what is one side effect you would expect from this drug and what is the reason for
the side effect (note: side effects are called “side effects” because they are NOT directly
related to the intended purpose of the treatment)?
A GnRH antagonist would also block the release of LH from the anterior pituitary. Since
LH stimlates testosterone production in the testes, males undergoing this treatment would
experience a sharp decline in T levels, leading to a number of effects (which would be
undesirable to most males…).
Hormone level
23. Unlike humans, many animals breed seasonally. For example, white-crowned sparrows
breed in the spring; during the rest of the year, they do not attempt to copulate, do not produce
sperm, and sing much less than normal (singing can be thought of as a secondary sexual
character). Using a solid line for testosterone and a dotted line for LH, draw a graph of the
expected male white-crowned sparrow hormonal profile over the course of a year.
Winter
Spring
Summer
Fall
24. In the box provided, indicate whether the value on the left is equal to (=), less than (<) or
greater than (>) the value on the right. The first one is done for you as an example.
Estrogen levels in typical
female mammals
>
Estrogen levels in typical
male mammals
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Review Questions 3/5/2001
LH in a normal, untreated
man
>
LH in the plasma of a man
following a large injection
of testosterone
GnRH levels in the pituitary
portal vein
>
GnRH levels in the
systemic circulation
FSH levels shortly before
ovulation in a normal
female
<
FSH levels in a female
whose ovaries have been
removed
Progesterone levels before
ovulation in a normal
female
<
Progesterone levels
following ovulation in a
normal female
GnRH levels in an
individual with androgen
insensitivity syndrome
(TFM)
=
GnRH levels in an normal
individual whose gonads
have been removed
25. The growth of certain breast cancers in women is estrogen-dependent. One drug used to treat
such breast cancers is Femara (letrozole). Femara acts by inhibiting the enzyme aromatase,
which converts testosterone to estrogen. The use of Femara is restricted to postmenopausal
women, however. What side effects might you expect in a woman of childbearing age who took
the drug Femara (name two)?
Increased growth of body hair growth, muscle growth (both due to increase testosterone
levels).
26. Some reproductive biology researchers are investigating a technique whereby female
mammals are injected with inhibin in order to produce an immune response. Once this treatment
takes place, the females produce antibodies that bind to and promote the degradation of the
natural inhibin released by the ovaries. In one sentence, what effect would you expect this
immune response to have on fertility in treated females?
Since inhibin inhibits release of FSH from the pituitary, the immune response would
reduce the effect of inhibin, thereby increasing FSH and likely increasing the number of
developing follicles.
27. Fill in the blanks with arrows indicating whether the level of the indicated hormone would
be normal (=), higher than normal (↑) or lower than normal (↓) in each of the following cases
:
Woman with a
tumor that results in
a non-functioning
anterior pituitary
Man whose testes
GnRH
Higher
FSH/LH
Lower
Gonadal steroids
Lower
Higher
Higher
Lower
8
are removed due to
testicular cancer
Woman with a
hypothalamic tumor
that results in oversecretion of GnRH
Man with a tumor
that completely
blocks blood flow
down the pituitary
portal vein
Review Questions 3/5/2001
Higher
Normal
Normal
Higher
Lower
Lower