Beruflich Dokumente
Kultur Dokumente
10 9 8 7 6 5 4 3 2 1
Keywords
allosterically modulated, transmembrane, covalent modulation, ligand-
gated, ion channels, depolarized, voltage-gated, refractory period, patch
clamp, myelin, nodes of Ranvier, secretory vesicles, skeletal muscle, motor
neurons, acetylcholine, sarcomere, striated, longitudinal sections, cross
sections, actin, myosin, troponin, tropomyosin, T-tubules, hypertrophy,
hyperplasia, performance-enhancing drugs, short-term memory, long-
term memory, sensoryneurons, synapse, cAMP, PKA, MAPK
Contents
Preface...................................................................................................ix
Acknowledgments....................................................................................xi
Introduction.........................................................................................xiii
Chapter 1 Neurons Receive and Send Information.............................1
Chapter 2 Muscles Contract and Grow Bigger..................................21
Ethical, Legal, and Social Implications: Use of
Performance Enhancing Drugs.....................................29
Chapter 3 Memories Require New Proteins in Neurons....................33
Ethical, Legal, and Social Implications: Concerns
About Memory Research..............................................41
Conclusion............................................................................................45
Glossary................................................................................................47
Index....................................................................................................49
Preface
This book about neurons and muscles is part of a thirty book series that
collectively surveys all of the major themes in biology. Rather than just
present information as a collection of facts, the reader is treated more like
a scientist, which means the data behind the major themes are presented.
Reading any of the thirty books by Campbell and Paradise provides read-
ers with biological context and comprehensive perspective so that readers
can learn important information from a single book with the potential to
see how the major themes span all size scales: molecular, cellular, organ-
ismal, population and ecologic systems. The major themes of biology en-
capsulate the entire discipline: information, evolution, cells, homeostasis
and emergent properties.
In the twentieth century, biology was taught with a heavy emphasis
on long lists of terms and many specific details. All of these details were
presented in a way that obscured a more comprehensive understanding.
In this book, readers will learn how neurons and muscles work and some
of the supporting evidence behind our understanding. Instead of believ-
ing or simply accepting information, readers of this book will learn about
the science behind the production of proteins the way professional scien-
tists dowith experimentation and data analysis. In short, data are put
back into the teaching of biological sciences.
Readers of this book who wish to see the textbook version of this
content can go to www.bio.davidson.edu/icb where they will find
pedagogically-designed and interactive Integrating Concepts in Biology for
introductory biology college courses or a high school AP Biology course.
Acknowledgments
Publishing this book would not have been possible without the generous
gift of Dr. David Botstein who shared some of his Breakthrough Prize
with AMC. Davids gift allowed us to hire talented artists (Tom Webster
and his staff at Lineworks, Inc.) and copyeditor Laura Loveall. Thanks go
to Kristen Mandava for project management and guidance on the pub-
lishing process. In particular, we are indebted to Katie Noble and Melissa
Hayban for their many hours of help and attention to detail.
Kristen Eshleman, Paul Brantley, Bill Hatfield and Olivia Booker
helped us with technology at Davidson College. We are grateful to ad-
ministrators Tom Ross, Clark Ross, Carol Quillen, Wendy Raymond,
Verna Case, and Barbara Lom who had confidence in us and encouraged
us to persist despite setbacks along the way.
These books were the product of the shared labor of my two vision-
ary coauthors Laurie Heyer and Chris Paradise. We shared the dream
and the hardships and developed this book from scratch. My family has
been very supportive and I thank Susan, Celeste and Paulina for their
support and patience. I also want to thank Jan Serie, my pedagogical
mentor, who taught me so much about the art and science of helping stu-
dents learn. I benefited from the support of the Howard Hughes Medi-
cal Institute grant 52006292, the James G. Martin Genomics Program,
and Davidson College. This book would not have survived its first draft
without my students who endured the typos and the early versions of this
book. These undergraduates participated in a bold experiment to see if
beginners could construct their own knowledge, retain what they learned,
and transform the way they see themselves and the discipline of biology.
While many people said that beginning students were not up to the task,
my students proved them wrong.
Introduction
This book focuses on neurons and muscles. In many ways, cells are similar
to computers. Cells and computers both work from a set of directions and
respond to inputs. Both store information, come in a variety of shapes,
consume energy, use electricity to function, and both can be infected by
viruses. Over time, humans have engineered smaller and smaller comput-
ers to the point that cells have been built to function as computers. The
next generation of computers will include human cells that have been
programmed with DNA and can be implanted into humans to aug-
ment our current functions. This chapter looks at two major functions
of neuronscommunication to another cell and memory formation.
A muscle contracts when it receives the appropriate signal from a neuron.
Neurons can communicate information over long distances very quickly.
Muscles process the output from a neuron and convert that informa-
tion into a contraction that can lead to larger muscles. Neurons encode
memory by depositing new proteins that alter the cells function to benefit
the organism.
CHAPTER 1
At birth, all newborns know how to move their muscles (Figure 1). They
kick, scream, and nurse instinctively. Although they can move their mus-
cles from the first minute of life, they do not have to consciously think
about the cellular actions required to move their muscles. All they have
to do is tell their body to respond, and it does. How fast can nerve cells
work? In the blink of an eye. The desire to blink tells the muscles that
control the eyelids to contract and relax in a matter of milliseconds. Since
diffusion alone is too slow to transmit the blink command from the
brain to the eyelid muscles, cells must use a different mechanism for com-
munication. The desire to blink starts as a chemical signal that stimulates
a nerve whichextends to the eyelid muscles. The neuron, or nerve cell,
receives the chemical input and converts the signal to an electrical cur-
rent that races down the axon to its terminal adjacent to the muscle cell.
At the neuromuscular junction, the neuron converts the electrical signal
back into a chemical message that is transmitted a very short distance
to the muscle, which interprets the information and contracts. The pro-
duction of cellular electricity begins with a modified version of signal
transduction.
Before understanding the neurons signal transduction, consider the
resting state of a neuron (Table 1). Cells do not maintain equal con-
centrations of ions inside and out. Because ions are charged particles,
they cannot pass through phospholipid bilayer membranes unassisted. In
most animal cells, more sodium ions (Na+) are excluded from the cyto-
plasm and accumulate in the extracellular environment. Conversely, cells
sequester more potassium ions (K+) in their cytoplasm than are typically
found outside the cells. Cells expend an enormous amount of energy to
2 NEURONS AND MUSCLES
phosphate group
2 potassium ions
cytoplasm
membrane
gamma beta
subunit subunit
A B extracellular
would diffuse into cells and potassium out of cells. The Na+/K+ pump
helps maintain the ion concentration gradients shown in Table 1. As with
many ion pumps, ATP is converted to adenosine diphosphate (ADP),
and the terminal phosphate is covalently added to the pump protein
on an aspartic acid, which is abbreviated D. The phosphate covalently
modulates the proteins shape and thus changes its function. The discov-
ery of the Na+/K+ pump was rewarded with a Nobel Prize, but it took
many more years to discover how the pump moves charged particles in
opposite directions across plasma membranes. Physiologists in the 1960s
slowly uncovered how the pump functioned. First, they added each ion
to the pump in the presence of radioactive ATP to determine which ion
stimulates the pumps phosphorylation. Only when sodium was added to
4 NEURONS AND MUSCLES
the cytoplasmic side of the pump did the pump bind to ATP and phos-
phorylate itself on the aspartic acid. Additional research over the next
20 years allowed physiologists and biochemists to completely diagram
how the Na+/K+ pump worked.
Neurons use electrical communication to move information down
their lengths as rapidly as possible. Chemical communication informs a
neuron what action it should take and what action it should pass on, such
as telling a muscle cell to contract. When neurons and muscles are resting,
they have thirty times more potassium in their cytoplasm than on the out-
side, and twelve times more sodium outside compared to inside. Na+/K+
pumps help maintain these ion gradients as a form of potential energy
that can be used later. For every ATP consumed, the Na+/K+ pump
moves three sodium ions out of the cell and two potassium ions into the
cell. This 3:2 ratio is a vital ion ratio because it contributes to the electrical
potential every animal cell on the planet needs to perform a wide range
of functions. By exporting one more Na+ than K+ it imports with each
Na+/K+ pump cycle, the cytoplasm gradually becomes more negative
compared to the extracellular world. One ion at a time, cells accumulate
an overall membrane potential, which is a separation of charged particles
in the form of Na+ and K+ ions. Animal cells have a resting membrane
potential in the range of 20 to 200 millivolts (mV), although the
precise number varies by cell type and species. The membrane potential
is also substantially maintained by a series of K+ ion leak channels not
discussed in this book.
Neurons that communicate to muscle cells at the neuromuscular junc-
tion have a resting membrane potential of approximately 70 mV, but
neurons are not resting to maintain these ion gradients. The membrane
potential is caused by a polarization of ions. All animal cells spend about
half of their energy maintaining ion gradients, so it may seem like an oxy-
moron to call these resting membrane potentials. When neurons are not
using electrical communication, they are described as resting, and the lack
of electrical activity is what is meant by resting membrane potential.
The Na+/K+ pump changes its shape in response to covalent modula-
tion when it is phosphorylated or dephosphorylated. Figure 3 illustrates
the steps. The pump (1) is allosterically modulated when it binds three so-
dium ions (2), which leads to ATP binding and phosphorylation (3). Once
Neurons Receive and Send Information 5
Adenosine-PPP
1 P
ion pump
no ions 2 3
bound ion pump Adenosine-PP ion pump
3 Na+ 3 Na+ 3 Na+
(inside) bound bound
2 K+ (inside) 4
6 ion pump
ion pump 5 no ions
2 K+ bound bound
ion pump
2 K+ P 3 Na+
bound (outside)
P 2 K+ (outside)
pore
beta delta
alpha subunit subunit
subunit
alpha alpha
beta subunit subunit
subunit
extracellular
gamma
subunit pore
membrane
delta cytoplasm
subunit
alpha gamma
subunit subunit
open
extracellular closed extracellular ligand
cytoplasm cytoplasm
C D
input output
measure
neuron
A
applied
applied
current
current
+50 +50
potential (mV)
potential (mV)
membrane
membrane
time time
0 0
50 50
70 70
0 1 2 0 1 2
B time (ms) time (ms)
applied
current
time
current generator
input
axon of neuron
measure
output
applied
applied
applied
current
current
current
time time time
ions are more abundant outside a neuron, but once the membrane is lo-
cally depolarized to the threshold level or more, then the voltage-gated
sodium channels open. Like all proteins, these voltage-gated ion channels
do not know what is happening outside of their tiny local environment.
All they can sense is their structure as determined by the local charged
ions interacting with the side chains of their amino acids. Like ligand-
gated ion channels, voltage-gated ion channels behave like a drinking
fountain in that the fountain is always ready to let the water flow but the
fountain must be gated first. The voltage-gated ion channels are selective,
and the first wave of ion channels open to permit only Na+ ions to rush
into the neuron.
In Figure 5, threshold was approximately 50 mV, or a change of
+20 mV. At threshold depolarization, the voltage-gated sodium chan-
nels open, and they contribute further to the local depolarization until
the membrane potential is inverted to about +45 mV. Positive 45 mV
10 NEURONS AND MUSCLES
applied
current time
current generator
propogation
input
axon of neuron
measure #2
measure #3
0 1 2 3
time (milliseconds)
represents the full depolarization for the cell in Figure 5. In Figure 7, the
depolarization wave moved down the length of the axon, and at each
position, the membrane potential reached +45 mV. The magnitude of
the action potential exceeded the initial stimulating voltage (+20 mV)
because once threshold was reached in a local area, all of the neighbor-
ing voltage-gated sodium channels opened and the membrane potential
was made less negative, causing more voltage-gated sodium channels to
Neurons Receive and Send Information 11
cannot
open closed
extracellular Na+ channel extracellular K+ channel extracellular K+ channel
electrode
measures
current
electrode clamp
membrane patch
the vesicle becomes part of the plasma membrane and its contents are
completely outside the cell.
Every activated neuron goes through the same three steps: 1) receive
a chemical message; 2) produce an electrical current that causes an action
potential to move down the axon; and 3) produce a new chemical mes-
sage to secrete via exocytosis. Action potentials are waves of Na+ ions that
jump from one node of Ranvier to the next in myelinated neurons. At
the end of the axon, calcium floods the cytoplasm, which triggers regu-
lated exocytosis of the neurotransmitter chemical messenger. Nerve to
muscle communication is very complex, but every animal performs the
same process for every movement. The next chapter describes how similar
neurons and muscles are with regard to their shared use of action poten-
tials and ion concentration gradients.
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Neurons Receive and Send Information 19
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