BRS Cell Biology and Histology (Board Review)

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Cell Biology
and Histology
SEVENTH EDITION

Leslie P. Gartner, PhD

Professor of Anatomy (Retired)
Department of Biomedical Sciences
University of Maryland Dental School
Baltimore, Maryland

James L. Hiatt, PhD

Professor Emeritus
Department of Biomedical Sciences
University of Maryland Dental School
Baltimore, Maryland
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Library of Congress Cataloging-in-Publication Data

Gartner, Leslie P., 1943- author.
Cell biology and histology / Leslie P. Gartner, James L. Hiatt. — Seventh edition.
  p. ; cm. — (Board review series)
Includes bibliographical references and index.
ISBN 978-1-4511-8951-3 (paperback : alk. paper)
I. Hiatt, James L., 1934- author. II. Title. III. Series: Board review series.
[DNLM: 1. Histological Techniques—Outlines. 2. Cytological Techniques—Outlines. QS 18.2]
QM553
611'.018—dc23
2014018636

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 Preface

We were very pleased with the reception of the sixth edition of this book, as well as with
the many favorable comments we received from students who used it in preparation for
the USMLE Step 1 or as an outline and study guide for their histology and/or cell biology
courses in professional schools or undergraduate colleges.
Many of the chapters have been extensively revised and updated to incorporate current
information, and we have attempted to refine the content of the text to present material
emphasized on National Board Examinations as succinctly as possible while still retaining
the emphasis on the relationship between cell structure and function through the vehicle of
cell and molecular biology. A tremendous amount of material has been compressed into a
concise but highly comprehensive presentation, using some new and revised illustrations.
The relevancy of cell biology and histology to clinical practice is illustrated by the presence
of clinical considerations within each chapter as appropriate.
The greatest changes that occurred in the evolution of this book from its previous edi-
tion are that we have added many more clinical considerations and compressed informa-
tion into tabular form. We believe that these changes make this board review book more
interesting and pertinent and the presentation of material in tables conserves time in the
review process for medical students in their preparation for the USMLE Step 1.
We are sad to announce that Judy Strum, our coauthor throughout the first six editions
of this review book, decided to complete her retirement from the faculty of the University of
Maryland School of Medicine thereby withdrawing her participation in the preparation of
the current edition of this textbook.
As always, we welcome comments, suggestions, and constructive criticism of this book.
Please address all comments to [email protected]
Leslie P. Gartner, PhD
James L. Hiatt, PhD

iii
 Acknowledgments

We thank the following individuals for their help and support during the preparation of this
book: Crystal Taylor, our Acquisitions Editor; and Dana Battaglia and Amy Weintraub, our
product Development Editor(s), who helped us weave all of the loose ends into a seamless
whole.

iv
 Contents

Preface  iii
Acknowledgments iv

1. Plasma Membrane 1
I. Overview—The Plasma Membrane (Plasmalemma; Cell Membrane) 1
II. Fluid Mosaic Model of the Plasma Membrane 1
III. Plasma Membrane Transport Processes 5
IV. Cell-to-Cell Communication 7
V. Plasmalemma–Cytoskeleton Association 9
Review Test 12

2. Nucleus 15
I. Overview—The Nucleus 15
II. Nuclear Envelope 15
III. Nucleolus 18
IV. Nucleoplasm 18
V. Chromatin 19
VI. Chromosomes 20
VII. DNA 21
VIII. RNA 22
IX. Cell Cycle 25
X. Apoptosis (Programmed Cell Death) 28
XI. Meiosis 29
Review Test 31

3. Cytoplasm and Organelles 33

I. Overview—The Cytoplasm 33
II. Structural Components 33
III. Interactions among Organelles 49
Review Test 58

v
vi Contents

4. Extracellular Matrix 61
I. Overview—The Extracellular Matrix 61
II. Ground Substance 61
III. Fibers 64
Review Test 72

5. Epithelia and Glands 75

I. Overview—Epithelia 75
II. Lateral Epithelial Surfaces 77
III. Basal Epithelial Surfaces 80
IV. Apical Epithelial Surfaces 83
V. Glands 87
Review Test 89

6. Connective Tissue 92
I. Overview—Connective Tissue 92
II. Extracellular Matrix 92
III. Connective Tissue Cells 93
IV. Classification of Connective Tissue 99
Review Test 103

7. Cartilage and Bone 106

I. Overview—Cartilage 106
II. Overview—Bone 110
III. Joints 120
Review Test 121

8. Muscle 124
I. Overview—Muscle 124
II. Structure of Skeletal Muscle 124
III. Contraction of Skeletal Muscle 130
IV. Innervation of Skeletal Muscle 132
V. Cardiac Muscle 133
VI. Smooth Muscle 135
VII. Contractile Nonmuscle Cells 139
Review Test 140
 Contents vii

9. Nervous System 143

I. Overview—Nervous System 143
II. Histogenesis of the Nervous System 143
III. Cells of Nervous System 145
IV. Synapses 151
V. Nerve Fibers 152
VI. Nerves 153
VII. Ganglia 155
VIII. Histophysiology of Nervous System 155
IX. Somatic Nervous System and Autonomic Nervous System 157
X. Central Nervous System 158
XI. Degeneration and Regeneration of Nerve Tissue 160
Review Test 162

10. Blood and Hemopoiesis 166

I. Overview—Blood 166
II. Blood Constituents 166
III. Blood Coagulation 172
IV. Bone Marrow 174
V. Prenatal Hemopoiesis 175
VI. Postnatal Hemopoiesis 175
VII. Hemopoietic Growth Factors (Csfs) 179
Review Test 181

11. Circulatory System 184

I. Overview—Blood Vascular System 184
II. Overview—Lymphatic Vascular System 195
Review Test 196

12. Lymphoid Tissue 199

I. Overview—The Lymphoid (Immune) System 199
II. Cells of the Immune System 201
III. Antigen Presentation and the Role of MHC Molecules 209
IV. Immunoglobulins 210
V. Diffuse Lymphoid Tissue 211
VI. Lymphoid Organs 212
Review Test 218
viii Contents

13. Endocrine System 221

I. Overview—The Endocrine System 221
II. Hormones 221
III. Overview—Pituitary Gland (Hypophysis) and Hypothalamus 222
IV. Overview—Thyroid Gland 228
V. Parathyroid Glands 232
VI. Overview—Adrenal (Suprarenal) Glands 234
VII. Pineal Gland (Pineal Body, Epiphysis) 237
Review Test 239

14. Skin 242

I. Overview—The Skin 242
II. Epidermis 242
III. Dermis 248
IV. Glands in the Skin 249
V. Hair, Hair Follicle, and Arrector Pili Muscle 251
VI. Nails 252
Review Test 254

15. Respiratory System 257

I. Overview—The Respiratory System 257
II. Conducting Portion of the Respiratory System 257
III. Overview—Respiratory Portion of the Respiratory System 262
IV. Lung Lobules 269
V. Pulmonary Vascular Supply 269
VI. Pulmonary Nerve Supply 269
Review Test 270

16. Digestive System: Oral Cavity

and ­Alimentary Tract 273
I. Overview—The Digestive System 273
II. Oral Region 273
III. Divisions of the Alimentary Canal 278
IV. Digestion and Absorption 289
Review Test 291
 Contents ix

17. Digestive System: Glands 294

I. Overview—Extrinsic Glands of the Digestive System 294
II. Major Salivary Glands 294
III. Overview—Pancreas 296
IV. Liver 299
V. Gallbladder 304
Review Test 306

18. The Urinary System 309

I. Overview—The Urinary System 309
II. Kidneys 309
III. Uriniferous Tubules 310
IV. Renal Blood Circulation 320
V. Regulation of Urine Concentration 321
VI. Excretory Passages 324
Review Test 327

19. Female Reproductive System 330

I. Overview—Female Reproductive System 330
II. Ovaries 330
III. Oviducts (Fallopian Tubes) 338
IV. Uterus 339
V. Cervix 341
VI. Fertilization and Implantation 342
VII. Placenta 343
VIII. Vagina 345
IX. External Genitalia (Vulva) 345
X. Mammary Glands 346
Review Test 348

20. Male Reproductive System 350

I. Overview—Male Reproductive System 350
II. Testes 350
III. Genital Ducts 357
IV. Accessory Genital Glands 359
V. Urethra 361
VI. Penis 362
Review Test 363
x Contents

21. Special Senses 366

I. Overview—Special Sense Receptors 366
II. Specialized Diffuse Receptors 366
III. Sense of Sight—Eye 368
IV. Sense of Hearing—Ear (Vestibulocochlear Apparatus) 378
Review Test 384

Comprehensive Examination 387

Index 405
 chapter
1 Plasma Membrane

I. OVERVIEW—THE PLASMA MEMBRANE (PLASMALEMMA;

CELL MEMBRANE)
A. Structure. The plasma membrane is approximately 7.5 nm thick and consists of two leaflets,
known as the lipid bilayer that houses associated integral and peripheral proteins.
1. The inner leaflet of the plasma membrane faces the cytoplasm, and the outer leaflet faces the
extracellular environment.
2. When examined by transmission electron microscopy, the plasma membrane displays a
trilaminar (unit membrane) structure.

B. Function
1. The plasma membrane envelops the cell and maintains its structural and functional integrity.
2. It acts as a semipermeable membrane between the cytoplasm and the external environment.
3. It permits the cell to recognize macromolecules and other cells as well as to be recognized by
other cells.
4. It participates in the transduction of extracellular signals into intracellular events.
5. It assists in controlling interaction between cells.
6. It maintains an electrical potential difference between the cytoplasmic and extracellular sides.

II. FLUID MOSAIC MODEL OF THE PLASMA MEMBRANE

A. The lipid bilayer (Figures 1.1, 1.2, and 1.3) is freely permeable to small, lipid-soluble, nonpolar
molecules but is impermeable to charged ions.
1. Molecular structure. The lipid bilayer is composed of phospholipids, glycolipids, and
cholesterol, of which, in most cells, phospholipids constitute the highest percentage.
a. Phospholipids are amphipathic molecules, consisting of one polar (hydrophilic) head and
two nonpolar (hydrophobic) fatty acyl tails, one of which is usually unsaturated.
b. The two leaflets are not identical; instead the distribution of the various types of
phospholipids is asymmetrical.
(1) The polar head of each molecule faces the membrane surface, whereas the tails project
into the interior of the membrane, facing each other.
(2) The tails of the two leaflets are mostly 16 to 18 carbon chain fatty acids, and they form
weak noncovalent bonds that attach the two leaflets to each other.

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Carbohydrate bound Integral proteins

to lipid and protein

Oligosaccharide
Polar head
Outer leaflet
Inner leaflet
Fatty acyl tail
Peripheral Integral
protein protein

FIGURE 1.1. The plasma membrane showing the outer (top) and inner (bottom) leaflets of the unit membrane. The
­hydrophobic fatty acyl tails and the polar heads of the phospholipids constitute the lipid bilayer. Integral proteins are
embedded in the lipid bilayer. Peripheral proteins are located primarily on the cytoplasmic aspect of the inner leaflet and
are attached by noncovalent interactions to integral proteins.

c. Glycolipids are restricted to the extracellular aspect of the outer leaflet. Polar carbohydrate
residues of glycolipids extend from the outer leaflet into the extracellular space and form
part of the glycocalyx.
d. Cholesterol, constituting 2% of plasmalemma lipids, is present in both leaflets, and helps
maintain the structural integrity of the membrane.

FIGURE 1.2. Photomicrograph of a collecting duct of the kidney displaying tall columnar cells. The arrows indicate the cell
membranes where two cells contact each other (×1,323).

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 Chapter 1 Plasma Membrane 3

M
M

FIGURE 1.3. Transmission electron micrograph of the basal region of a columnar cell from a kidney-collecting tubule.
The basal cell membrane forms numerous complex folds to increase its surface area. M, mitochondria; red arrowheads,
plasmalemma; red arrow, basal lamina (×28,435).

e. Microdomains of the cell membrane rich in cholesterol and glycosphingolipids are less
fluid and thicker than the surrounding cell membrane, and are known as lipid rafts.
2. Fluidity of the lipid bilayer is crucial to exocytosis, endocytosis, membrane trafficking, and
membrane biogenesis.
a. Fluidity increases with increased temperature and with decreased saturation of the fatty
acyl tails.
b. Fluidity decreases with an increase in the membrane's cholesterol content.

B. Membrane proteins (see Figure 1.1) include integral proteins and peripheral proteins and, in most
cells, constitute approximately 50% of the plasma membrane composition.
1. Integral proteins are dissolved in the lipid bilayer.
a. Transmembrane proteins span the entire thickness of the plasma membrane and may
function as membrane receptors, enzymes, cell adhesion molecules, cell recognition
proteins, molecules that function in message transduction, and transport proteins.
(1) Most transmembrane proteins are glycoproteins.
(2) Transmembrane proteins are amphipathic and contain hydrophilic and hydrophobic
amino acids, some of which interact with the hydrocarbon tails of the membrane
phospholipids.
(3) Most transmembrane proteins are folded, so that they pass back and forth across the
plasmalemma; therefore, they are also known as multipass proteins.
b. Integral proteins may also be anchored to the inner (or occasionally outer) leaflet via fatty
acyl or prenyl groups.
c. In freeze-fracture preparations, integral proteins remain preferentially attached to the
P-face, the outer (protoplasmic face) surface of the inner leaflet, rather than the E-face
(extracellular face) (Figure 1.4).
2. Peripheral proteins do not extend into the lipid bilayer.
a. These proteins are located on the cytoplasmic as well as on the extracellular aspects of the
cell membrane.
b. The outer leaflets of some cells possess covalently linked glycolipids to which peripheral
proteins are anchored; these peripheral proteins thus project into the extracellular space.

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1 2

4
3

A
FIGURE 1.4. Freeze-fracturing cleaves the plasma membrane (5). The impressions (2) of the transmembrane proteins are
evident on the E-face between the inner (3) and outer leaflets (4). The integral proteins (1) remain preferentially attached
to the P-face (A), the external surface of the inner leaflet; fewer proteins remain associated with the E-face (B), the inter-
nal surface of the outer leaflet. The arrowhead indicates a transmembrane protein attached to both E-face and P-face.
(Reprinted with permission from Krstic RV. Ultrastruktur der Saugertierzelle. Berlin, Germany: Springer Verlag; 1976:177.)

c. Frequently, carbohydrates may bind to the peripheral proteins on the extracellular aspect
of the plasmalemma; these glycogen groups are referred to as glycoproteins.
d. Peripheral proteins bind to the phospholipid polar groups or integral proteins of the
membrane via noncovalent interactions.
e. They usually function as electron carriers (e.g., cytochrome c) part of the cytoskeleton or as
part of an intracellular second messenger system.
f. They include a group of anionic, calcium-dependent, lipid-binding proteins known as
annexins, which act to modify the relationships of other peripheral proteins with the lipid
bilayer and also to function in membrane trafficking and the formation of ion channels;
synapsin I, which binds synaptic vesicles to the cytoskeleton; and spectrin, which stabilizes
cell membranes of erythrocytes.
3. Functional characteristics of membrane proteins
a. The lipid-to-protein ratio (by weight) in plasma membranes ranges from 1:1 in most cells to
as much as 4:1 in myelin.
b. Some membrane proteins diffuse laterally in the lipid bilayer; others are immobile and are
held in place by cytoskeletal components.

C. Glycocalyx (cell coat), located on the outer surface of the outer leaflet of the plasmalemma, varies
in appearance (fuzziness) and thickness (up to 50 nm).
1. Composition. The glycocalyx consists of polar oligosaccharide side chains linked covalently to
most proteins and some lipids (glycolipids) of the plasmalemma. It also contains proteoglycans
(glycosaminoglycans bound to integral proteins).
2. Function
a. The glycocalyx aids in attachment of some cells (e.g., fibroblasts but not epithelial cells) to
extracellular matrix components.
b. It binds antigens and enzymes to the cell surface.
c. It facilitates cell–cell recognition and interaction.
d. It protects cells from injury by preventing contact with inappropriate substances.
e. It assists T cells and antigen-presenting cells in aligning with each other in proper fashion
and aids in preventing inappropriate enzymatic cleavage of receptors and ligands.
f. In blood vessels, it lines the endothelial surface to decrease frictional forces as the blood
rushes by and it also diminishes loss of fluid from the vessel.

D. Lipid rafts, as mentioned above, are microdomains of the plasma membrane that are thicker
than the surrounding plasma membrane, and for this reason they protrude slightly into the

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 Chapter 1 Plasma Membrane 5

extracellular space. Because of their higher cholesterol concentration and because they are rich
in glycosphingolipids, they are less fluid than the surrounding cell membrane. Some of these
lipid rafts have integral and peripheral proteins associated with them and they function in cell
signaling. Different lipid rafts may specialize as specific signaling processes, thus separating the
various signaling modalities and enhancing the possibility of the occurrence of specific signaling
events.

III. PLASMA MEMBRANE TRANSPORT PROCESSES

These processes include transport of a single molecule (uniport) or cotransport of two different mol-
ecules in the same (symport) or opposite (antiport) direction.

A. Passive transport (Figure 1.5) includes simple and facilitated diffusion. Neither of these processes
requires energy because molecules move across the plasma membrane down a concentration or
electrochemical gradient.
1. Simple diffusion transports small nonpolar molecules (e.g., O2 and N2) and small, uncharged,
polar molecules (e.g., H2O, CO2, and glycerol). It exhibits little specificity, and the diffusion rate
is proportional to the concentration gradient of the diffusing molecule.
2. Facilitated diffusion occurs via ion channels and/or carrier proteins, structures that exhibit
specificity for the transported molecules. Not only is it faster than simple diffusion but it is also
responsible for providing a pathway for ions and large polar molecules to traverse membranes
that would otherwise be impermeable to them.
a. Ion channel proteins are multipass transmembrane proteins that form small aqueous pores
across membranes through which specific small water-soluble molecules and ions, such as
Cl−, pass down an electrochemical gradient (passive transport).
b. Aquaporins are channels designed for the rapid transport of water across the cell membrane
without permitting an accompanying flow of protons to pass through the channels. They
accomplish this by forcing the water molecules to flip-flop halfway down the channel, so
that water molecules enter aquaporins with their oxygen leading into the channel and leave
with their oxygen trailing the hydrogen atoms.
c. Carrier proteins are multipass transmembrane proteins that undergo reversible
conformational changes to transport specific molecules across the membrane; these
proteins function in both passive transport and active transport.

Exterior

Interior
Simple Ion channel– Carrier protein–
diffusion mediated mediated
diffusion diffusion

FIGURE 1.5. Passive transport of molecules across plasma membranes by simple diffusion (left) and by either of the two
types of facilitated diffusion mediated by ion channel proteins (center) and carrier proteins (right).

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CLINICAL
 ystinuria is a hereditary condition caused by abnormal carrier proteins that
C
CONSIDERATIONS are unable to remove cystine from the urine, resulting in the formation of
kidney stones.
Cystic fibrosis is a hereditary disease involving a mutation in the cystic fibrosis transmembrane
­conductance regulator (CFTR) gene that produces malformed chloride channel proteins that are
­unable to transport chloride ions, causing an increase in the entry of Na+ ions into the cell. The
higher intracellular concentration of NaCl increases the flow of water into the cell, and the mucin
that is released into the extracellular environment cannot become normally hydrated, thus m ­ aking
the mucus thicker than normal, which obstructs the very small bronchiolar passageways of the
lungs. As the disease progresses, infections result, the lungs become unable to function properly,
and the individual succumbs to the disease and dies.

B. Active transport is an energy-requiring process that transports a molecule against an

electrochemical gradient via carrier proteins.
1. Na∙–K∙ pump
a. Mechanism. The Na+–K+ pump involves the antiport transport of Na+ and K+ ions mediated
by the carrier protein, Na∙–K∙ adenosine triphosphatase (ATPase).
(1) Three Na+ ions are pumped out of the cell and two K+ ions are pumped into the cell.
(2) The hydrolysis of a single adenosine triphosphate (ATP) molecule by the Na+–K+ ATPase
is required to transport five ions.
b. Function
(1) The primary function is to maintain constant cell volume by decreasing the intracellular
ion concentration (and thus the osmotic pressure) and increasing the extracellular ion
concentration, thus decreasing the flow of water into the cell.
(2) The Na+–K+ pump also plays a minor role in the maintenance of a potential difference
across the plasma membrane.
2. Glucose transport involves the symport movement of glucose across an epithelium
(transepithelial transport). Transport is frequently powered by an electrochemical Na+
gradient, which drives carrier proteins located at specific regions of the cell surface.
3. ATP-binding cassette transporters (ABC transporters) are transmembrane proteins that have
two domains, the intracellularly facing nucleotide-binding domain (ATP-binding domain) and
the membrane-spanning domain (transmembrane domain). In eukaryotes, ABC transporters
function in exporting materials, such as toxins and drugs, from the cytoplasm into the
extracellular space, using ATP as an energy source. ABC transporters may have additional
functions, such as those of the placenta, which presumably protect the developing fetus from
xenobiotics, macromolecules such as antibiotics, not manufactured by cells of the mother.

CLINICAL
Multidrug-resistant (MDR) proteins are ABC transporters that are present
CONSIDERATIONS in certain cancer cells that are able to transport the cytotoxic drugs admin-
istered to treat the malignancy. It has been shown that in more than one-third of the cancer patients,
the malignant cells develop MDR proteins that interfere with the treatment modality being used.

C. Facilitated diffusion of ions can occur via ion channel proteins or ionophores.
1. Selective ion channel proteins permit only certain ions to traverse them.
a. K+ leak channels are the most common ion channels. These channels are ungated and leak
K+, the ions most responsible for establishing a potential difference across the plasmalemma.
b. Gated ion channels open only transiently in response to various stimuli. They include the
following types:
(1) Voltage-gated channels open when the potential difference across the membrane
changes (e.g., voltage-gated Na+ channels, which function in the generation of action
potentials; see Chapter 9 VIII B 1 e).
(2) Mechanically gated channels open in response to a mechanical stimulus (e.g., the
tactile response of the hair cells in the inner ear).

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(3) Ligand-gated channels open in response to the binding of a signaling molecule or ion.
These channels include neurotransmitter-gated channels, nucleotide-gated channels,
and G protein–gated K+ channels of cardiac muscle cells.

CLINICAL
Ligand-gated ion channels are probably the location where anesthetic
CONSIDERATIONS agents act to block the spread of action potentials.

2. Ionophores are lipid-miscible molecules that form a complex with ions and insert into the
lipid bilayer to transport those ions across the membrane. There are two ways in which they
perform this function:
a. They enfold the ion and pass through the lipid bilayer.
b. They insert into the cell membrane to form an ion channel whose lumen is hydrophilic.

Ionophores are frequently fed to cattle and poultry as antibiotic agents and growth-enhancing
substances.

IV. CELL-TO-CELL COMMUNICATION

A. Signaling molecules, secreted by signaling cells, bind to receptor molecules of target cells, and in
this fashion, these molecules function in cell-to-cell communication in order to coordinate
cellular activities. Examples of such signaling molecules that effect communications include
neurotransmitters, which are released into the synaptic cleft (see Chapter 8 IV A 1 b; Chapter 9 IV B 5);
endocrine hormones, which are carried in the bloodstream and act on distant target cells; and
hormones released into the intercellular space, which act on nearby cells (paracrine hormones) or on
the releasing cell itself (autocrine hormones).
1. Lipid-soluble signaling molecules penetrate the plasma membrane and bind to receptors
within the cytoplasm or inside the nucleus, activating intracellular messengers. Examples
include hormones that influence gene transcription.
2. Hydrophilic signaling molecules bind to and activate cell-surface receptors (as do some lipid-
soluble signaling molecules) and have diverse physiologic effects (see Chapter 13). Examples
include neurotransmitters and numerous hormones (e.g., serotonin, thyroid-stimulating
hormone, insulin).

B. Membrane receptors are primarily integral membrane glycoproteins. They are embedded
in the lipid bilayer and have three domains: an extracellular domain that protrudes into the
extracellular space and has binding sites for the signaling molecule, a transmembrane domain that
passes through the lipid bilayer, and an intracellular domain that is located on the cytoplasmic
aspect of the lipid bilayer and contacts either peripheral proteins or cellular organelles, thereby
transducing the extracellular contact into an intracellular event.

CLINICAL
Venoms, such as those of some poisonous snakes, inactivate acetylcho-
CONSIDERATIONS line receptors of skeletal muscle sarcolemma at neuromuscular junctions.
Autoimmune diseases may lead to the production of antibodies that specifically bind to and
­activate certain plasma membrane receptors. An example is Graves disease (hyperthyroidism)
(see Chapter 13 IV B).

1. Function
a. Membrane receptors control plasmalemma permeability by regulating the conformation of
ion channel proteins.
b. They regulate the entry of molecules into the cell (e.g., the delivery of cholesterol via
low-density lipoprotein receptors).
c. They bind extracellular matrix molecules to the cytoskeleton via integrins, which are
essential for cell–matrix interactions.

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d. They act as transducers to translate extracellular events into an intracellular response via
the second messenger systems.
e. They permit pathogens that mimic normal ligands to enter cells.
2. Types of membrane receptors (See Table 1.2).
a. Channel-linked receptors bind a signaling molecule that temporarily opens or closes the
gate, permitting or inhibiting the movement of ions across the cell membrane. Examples
include nicotinic acetylcholine receptors on the muscle-cell sarcolemma at the myoneural
junction (see Chapter 8 IV A).
b. Catalytic receptors are single-pass transmembrane proteins.
(1) Their extracellular moiety is a receptor and their cytoplasmic component is a protein
kinase.
(2) Some catalytic receptors lack an extracytoplasmic moiety and, as a result, are
continuously activated; such defective receptors are coded for by some oncogenes.
(3) Examples of catalytic receptors include the following:
(a) Insulin binds to its receptor, which autophosphorylates. The cell then takes up the
insulin–receptor complex by endocytosis, enabling the complex to function within
the cell.
(b) Growth factors (e.g., epidermal growth factor, platelet-derived growth factor) bind to
specific catalytic receptors and induce mitosis.
c. G protein–linked receptors are transmembrane proteins associated with an ion channel or
with an enzyme that is bound to the cytoplasmic surface of the cell membrane.
(1) These receptors interact with heterotrimeric G protein (guanosine triphosphate [GTP]-
binding regulatory protein) after binding of a signaling molecule. The heterotrimeric G
protein is composed of three subunits: `, a, and f complex. The binding of the signaling
molecule causes either
(a) the dissociation of the ` subunit from the β and γ complex where the α subunit
interacts with its target or
(b) the three subunits do not dissociate, but either the ` subunit and/or the β and γ
complex become activated and can interact with their targets.
This interaction results in the activation of intracellular second messengers, the most
common of which are cyclic adenosine monophosphate (cAMP), Ca2+, and the inositol
phospholipid–signaling pathway.
(2) Examples include the following:
(a) Heterotrimeric G proteins (Table 1.1), which are folded in such a fashion that they
make seven passes as they penetrate the cell membrane. These are stimulatory
G protein (Gs) (Figure 1.6); inhibitory G protein (Gi); phospholipase C activator
G protein (Gq); olfactory-specific G protein (Golf); transducin (Gt); Go, which acts to
open K+ channels and close Ca2+ channels; and G12/13, which controls the formation
of the actin component of the cytoskeleton and facilitates migration of the cell.
(b) Monomeric G proteins (low-molecular-weight G proteins) are small single-chain
proteins that also function in signal transduction.
1. Various subtypes resemble Ras, Rho, Rab, and ARF proteins.
2. These proteins are involved in pathways that regulate cell proliferation and
differentiation, protein synthesis, attachment of cells to the extracellular matrix,
exocytosis, and vesicular traffic.

CLINICAL
Cholera toxin is an exotoxin produced by the bacterium Vibrio cholerae
CONSIDERATIONS that alters Gs protein, so that it is unable to hydrolyze its GTP ­molecule.
As a result, cAMP levels increase in the surface-absorptive cells of the intestine, leading to
­excessive loss of electrolytes and water and severe diarrhea.
Pertussis toxin, the product of the bacterium that causes whooping cough, inserts ADP-ribose
into the α subunits of trimeric G proteins, causing the accumulation of the inactive form of G proteins
­resulting in irritation of the mucosa of the bronchial passages.
Defective Gs proteins may lead to mental retardation, diminished growth and sexual development,
and decreased responses to certain hormones.

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 Chapter 1 Plasma Membrane 9

t a b l e 1.1 Functions and Examples of Heterotrimeric G Proteins

Type Function Result Examples

Gs Activates adenylate cyclase, Activation of protein kinases Binding of epinephrine to

leading to formation of cAMP β-adrenergic receptors increases
cAMP levels in cytosol
Gi Inhibits adenylate cyclase, Protein kinases remain inactive Binding of epinephrine to
preventing formation of cAMP α2-adrenergic receptors
decreases cAMP levels in cytosol
Gq Activates phospholipase C, Influx of Ca2+ into cytosol and Binding of antigen to
leading to formation of inositol activation of protein kinase C membrane-bound IgE causes the
triphosphate and diacylglycerol release of histamine by mast cells
Go Opens K+ channels and closes Inhibits adenylate cyclase Inducing contraction of smooth
Ca2+ channels Influx of K+ and limits Ca2+ muscle
movement
Golf Activates adenylate cyclase in Opens cAMP-gated Na+ Binding of odorant to
olfactory neurons channels G protein–linked receptors initiates
generation of nerve impulse
Gt Activates cGMP Hyperpolarization of rod cell Photon activation of rhodopsin
phosphodiesterase in rod cell membrane causes rod cells to fire
membranes, leading to hydrolysis
of cGMP
G12/13 Activates Rho family of guanosine Regulates cytoskeleton assembly Facilitating cellular migration
triphosphatases by controlling actin formation

cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; IgE, immunoglobulin E.

Signaling
molecule

Exterior Receptor Adenylate

cyclase

Activation
R Ad R Adc

Interior γ β α γ β α
cAMP ATP
GTP + GTP
PPi

FIGURE 1.6. Functioning of Gs protein–linked receptors. The signaling molecule binds to the receptor, which causes the
α-subunit of the Gs protein to bind guanosine triphosphate (GTP) and dissociate from the β and γ subunits. Activation of
adenylate cyclase by the GTP–α-subunit complex stimulates synthesis of cyclic adenosine monophosphate (cAMP), one
of the most common intracellular messengers.

V. PLASMALEMMA–CYTOSKELETON ASSOCIATION
The plasmalemma and cytoskeleton associate through integrins. The extracellular domain of inte-
grins binds to extracellular matrix components, and the intracellular domain binds to cytoskeletal
components. Integrins stabilize the plasmalemma and determine and maintain cell shape.

A. Red blood cells (Figure 1.7A) have integrins, called band 3 proteins, which are located in the
plasmalemma. The cytoskeleton of a red blood cell consists mainly of spectrin, actin, band
4.1 protein, and ankyrin.

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 10 BRS Cell Biology and Histology

Band 3

Actin oligomers Ankyrin Spectrin Band 4.1

A

Integrin
α β β α

Plasma
membrane

Talin Vinculin

α-Actinin

Actin
B

FIGURE 1.7. Plasmalemma–cytoskeleton association in red blood cells (A) and nonerythroid cells (B). (Adapted with permission
from Widnell CC, Pfenninger KH. Essential Cell Biology. Baltimore, MD: Williams & Wilkins; 1990:82.)

1. Spectrin is a long, flexible protein (about 110 nm long), composed of an `-chain and a a-chain,
that forms tetramers and provides a scaffold for structural reinforcement.
2. Actin attaches to binding sites on the spectrin tetramers and holds them together, thus aiding
in the formation of a hexagonal spectrin latticework.
3. Band 4.1 protein binds to and stabilizes spectrin–actin complexes.
4. Ankyrin is linked to both band 3 proteins and spectrin tetramers, thus attaching the spectrin–
actin complex to transmembrane proteins.

B. The cytoskeleton of nonerythroid cells (Figure 1.7B) consists of the following major components:
1. Actin (and perhaps fodrin), which serves as a nonerythroid spectrin.
2. `-Actinin, which cross-links actin filaments to form a meshwork.
3. Vinculin, which binds to α-actinin and to another protein, called talin, which, in turn, attaches
to the integrin in the plasma membrane.

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 Chapter 1 Plasma Membrane 11

CLINICAL
1. Hereditary spherocytosis results from a defective spectrin that has
CONSIDERATIONS a decreased ability to bind to band 4.1 protein. The disease is
­characterized by fragile, misshapen red blood cells, or spherocytes; ­destruction of these
­spherocytes in the spleen leads to anemia.
2. During high-speed car accidents and often in shaken baby syndrome, the sudden
­accelerating and decelerating forces applied to the brain cause shearing damage to axons,
especially at the interface between white matter and gray matter. The stretching of the
­axons results in diffuse axonal injury, a widespread lesion whose consequence is the o­ nset
of a persistent coma from which only 10% of the affected individuals regain conscious-
ness. Examination of the affected tissue displays irreparable cleavage of spectrin, with
an ­ensuing destruction of the neuronal cytoskeleton, leading to loss of plasma membrane
integrity and eventual cell death.

t a b l e 1.2 Major Classes of Membrane Proteins

Major Class Functions

Receptor protein Recognizes and binds signaling molecule on the extracellular surface of the cell membrane
Enzyme Functions differ depending on the enzyme (e.g., energy utilization and digestion)
Pump Transports ions and small molecules across the cell membrane by the expenditure of energy
Channel Transports ions and small molecules across the cell membrane without the expenditure
of energy
Linker protein Functions in the attachment of the cell to the extracellular matrix
Structural protein Functions in attaching neighboring cells to each other

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 Review Test

Directions: Each of the numbered items or incomplete statements in this section is followed by
a­ nswers or by completions of the statement. Select the ONE lettered answer or completion that is
BEST in each case.

1. A herpetologist is bitten by a poisonous 5. Which one of the following substances is

snake and is taken to the emergency depart- unable to traverse the plasma membrane by
ment with progressive muscle paralysis. The simple diffusion?
venom is probably incapacitating his (A) O2
(A) Na+ channels. (B) N2
(B) Ca2+ channels. (C) Na+
(C) phospholipids. (D) Glycerol
(D) acetylcholine receptors. (E) CO2
(E) spectrin.
6. Symport refers to the process of transporting
2. Cholesterol functions in the plasmalemma (A) a molecule into the cell.
to (B) a molecule out of the cell.
(A) increase fluidity of the lipid bilayer. (C) two different molecules in opposite
(B) decrease fluidity of the lipid bilayer. directions.
(C) facilitate the diffusion of ions through the (D) two different molecules in the same
lipid bilayer. direction.
(D) assist in the transport of hormones across (E) a molecule between the cytoplasm and the
the lipid bilayer. nucleus.
(E) bind extracellular matrix molecules.
7. One of the ways that cells communicate with
3. The cell membrane consists of various com- each other is by secretion of various molecules.
ponents, including integral proteins. These The secreted molecule is known as
integral proteins (A) a receptor molecule.
(A) are not attached to the outer leaflet. (B) a signaling molecule.
(B) are not attached to the inner leaflet. (C) a spectrin tetramer.
(C) include transmembrane proteins. (D) an integrin.
(D) are preferentially attached to the E-face. (E) an anticodon.
(E) function in the transport of cholesterol-
based hormones. 8. Adrenocorticotropic hormone (ACTH) trav-
els through the bloodstream, enters connective
4. Which one of the following transport pro- tissue spaces, and attaches to specific sites on
cesses requires energy? target-cell membranes. These sites are
(A) Facilitated diffusion (A) peripheral proteins.
(B) Passive transport (B) signaling molecules.
(C) Active transport (C) G proteins.
(D) Simple diffusion (D) G protein–linked receptors.
(E) ribophorins.

12

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