membrane potentials

1. Membrane and Nerve Physiology

2.  composed primarily of phospholipids and
proteins
 impermeable to large molecules such as
proteins and nucleic acids, thus ensuring
their retention within the cytosol.
 It is selectively permeable to small
molecules such as ions and metabolites

3.  Selective transport of molecules into and out of the
cell. A function carried out by membrane transport
proteins.
 Cell recognition through the use of cell surface
antigens.
 Cell communication through neurotransmitter and
hormone receptors and through signal transduction
pathways.
 Tissue organization, such as temporary and
permanent cell junctions, and interaction with the
extracellular matrix, with the use of a variety of cell
adhesion molecules.
• Membrane-dependent enzymatic activity.
• Determination of cell shape by linkage of the
cytoskeleton to the plasma membrane

4.  The major lipids of the plasma membrane:
 a. phospholipids
 b. phosphoglycerides
 Phospholipids
 The majority of membrane phospholipids have a glycerol “backbone” to which
are attached the fatty acyl chains, and an alcohol is linked to glycerol via a
phosphate group.
 are amphipathic molecules that contain a charged (or polar) hydrophilic head
and two (nonpolar) hydrophobic fatty acyl chains.
 hydrophilic (water soluble) head,
 two fatty acid tails, which are hydrophobic (water insoluble)
 The amphipathic nature of the phospholipid molecule is critical for the
formation of the bilayer:
 The hydrophobic fatty acyl chains form the core of the bilayer
 the polar head groups are exposed on the surface

5.  Lipid-soluble substances
 e.g., O2 , CO2 , steroid hormones
 cross cell membranes because they can dissolve
in the hydrophobic lipid bilayer.
 Water-soluble substances
 e.g., Na+ , Cl− , glucose, H2 O
 cannot dissolve in the lipid of the membrane, but
may cross through water-filled channels, or
pores, or may be transported by carriers

7.  As much as 50% of the plasma membrane is composed of proteins.
classified as:
 A. integral, lipid-anchored,
 B. peripheral.
 Integral membrane proteins
 are imbedded in the lipid bilayer, where hydrophobic amino acid residues are
associated with the hydrophobic fatty acyl chains of the membrane lipids.
 include ion channels, transport proteins, receptors, and guanosine 5′-
triphosphate (GTP)–binding proteins (G proteins).
 Many integral membrane proteins span the bilayer; such proteins are termed
transmembrane proteins.
 Transmembrane proteins
 have both hydrophobic and hydrophilic regions.
 The hydrophobic region, often in the form of an α helix, spans the membrane.
 Hydrophilic amino acid residues are then exposed to the aqueous environment on
either side of the membrane.
 Transmembrane proteins may pass through the membrane multiple times.

8.  A protein can also be attached to the membrane
via lipid anchors.
 The protein is covalently attached to a lipid
molecule, which is then embedded in one leaflet
of the bilayer.
 Glycosylphosphatidylinositol (GPI) anchors
proteins to the outer leaflet of the membrane.
 Proteins can be attached to the inner leaflet via
their amino-terminus by fatty acids (e.g.,
myristate or palmitate) or via their carboxyl-
terminus by prenyl anchors (e.g., farnesyl or
geranylgeranyl).

9.  may be associated with the polar head groups of the membrane
lipids
 more commonly bind to integral or lipid-anchored proteins
 are not imbedded in the cell membrane.
 are not covalently bound to membrane components.
 are loosely attached to the cell membrane by electrostatic
interactions.

 In many cells, some of the outer leaflet lipids, as well as many of
the proteins exposed on the outer surface of the membrane, are
glycosylated (i.e., have short chains of sugars, called
oligosaccharides, attached to them).
 Collectively, these glycolipids and glycoproteins form what is
called the glycocalyx.
 Depending on the cell these glycolipids and glycoproteins may be
involved in cell recognition (e.g., cell surface antigens) and
formation of cell-cell interactions (e.g., attachment of
neutrophils to vascular endothelial cells)

11. 1. Tight junctions (zonula occludens)
■ are the attachments between cells (often
epithelial cells).
■ may be an intercellular pathway for solutes,
depending on the size, charge, and
characteristics of the tight junction.
■ may be “tight” (impermeable), as in the renal
distal tubule, or “leaky” (permeable), as in the
renal proximal tubule and gallbladder.
2. Gap junctions
■ are the attachments between cells that
permit intercellular communication.
■ for example, permit current flow and
electrical coupling between myocardial cells.

12.  water channels
 ion channels
 solute carriers
 adenosine triphosphate (ATP)–dependent
transporters

13. Water channels, or aquaporins (AQPs)
are the main routes for water movement into
and out of the cell.
They are widely distributed throughout the body
(e.g., the brain, lungs, kidneys, salivary glands,
gastrointestinal tract, and liver).
Cells express different AQP isoforms, and some
cells even express multiple isoforms
Each AQP molecule consists of six membrane-
spanning domains and a central water-
transporting pore.
Four AQP monomers assemble to form a
homotetramer in the plasma membrane, with
each monomer functioning as a water channel.

14.  Ion Channels
 are found in all cells
 especially important for the function of
excitable cells (e.g., neurons and muscle cells).
 classified by their selectivity, conductance and
mechanism of channel gating (i.e., opening and
closing).

15.  Selectivity
 is defined as the nature of the ions that pass through
the channel.
 At one extreme, ion channels can be highly selective,
in that they allow only a specific ion through.
 At the other extreme, they may be nonselective,
allowing all or a group of cations or anions through.
 Channel conductance
 refers to the number of ions that pass through the
channel and is typically expressed in picosiemens (pS).

16.  gating
 ion channels fluctuate between an open state or a
closed state
 Factors that can control gating include membrane
voltage, extracellular agonists or antagonists (e.g.,
acetylcholine is an extracellular agonist that controls
the gating of a cation-selective channel in the motor
end plate of skeletal muscle cells; intracellular
messengers (e.g., Ca++ , ATP, cyclic guanosine
monophosphate), and mechanical stretch of the
plasma membrane.
 Ion channels can be regulated by a change in the
number of channels in the membrane or by gating of
the channels

17.  represent a large group of membrane transporters categorized into more than 50
families
 These carriers can be divided into three groups according to their mode of
transport.
 uniporters (or facilitated transporters)
 transports a single molecule across the membrane.
 The transporter that brings glucose into the cell (glucose transporter 1 [GLUT-1], or
SLC2A1) is an important member of this group.
 symporters (or cotransporters),
 couples the movement of two or more molecules/ions across the membrane.
 As the name implies, the molecules/ions are transported in the same direction.
 The Na+ ,K+ ,2Cl− (NKCC) symporter found in the kidney (NKCC2, or SLC12A1), which is
crucial for diluting and concentrating the urine is a member of this group.
 antiporters (or exchange transporters)
 also couples the movement of two or more molecules/ions across the membrane;
 the molecules/ions are transported in opposite directions.
 The Na+ -H+ antiporter is a member of this group of solute carriers.
 One isoform of this antiporter (NHE-1, or SLC9A1) is found in all cells and plays an
important role in regulating intracellular pH

18.  use the energy in ATP to drive the movement of molecules/ ions across the membrane.
 There are two groups of ATPdependent transporters:
 ATPase ion transporters
 ATP-binding cassette (ABC) transporters.
 The ATPase ion transporters
 are subdivided into:
 P-type ATPases and V-type ATPases.
 A. The P-type ATPases
 are phosphorylated during the transport cycle.
 Na+ ,K+ -ATPase is an important example of a P-type ATPase.
 With the hydrolysis of each ATP molecule, it transports three Na+ ions out of the cell and two K+ ions into the cell.
 Na+ ,K+ -ATPase is present in all cells and plays a critical role in establishing cellular ion and electrical gradients, as well as
maintaining cell volume
 B. V-type H+ -ATPases
 are found in the membranes of several intracellular organelles (e.g., endosomes, lysosomes);
 as a result, they are also referred to as vacuolar H+ -ATPases.
 The H+ -ATPase in the plasma membrane plays an important role in urinary acidification

19. ABC transporters
-represent a large group of membrane transporters.
-are found in both prokaryotic and eukaryotic cells
-have amino acid domains that bind ATP (i.e., ABC domains).
-They transport a diverse group of molecules/ions, including Cl− , cholesterol, bile
acids, drugs, iron, and organic anions.
-Because biologically important molecules enter and leave cells through membrane
transporters, membrane transport is specific and regulated.
-Although some membrane transporters are ubiquitously expressed in all cells (e.g.,
Na+ ,K+ -ATPase), the expression of many other transporters is limited to specific
cell types.
-This specificity of expression tailors the function of the cell to the organ system in
which it is located (e.g., the sodium-glucose–linked transporters SGLT-1 and SGLT-2
in the epithelial cells of the intestines and renal proximal tubules).
In addition, the amount of a molecule being transported across the membrane can
be regulated.
Such regulation can take place through altering the number of transporters in the
membrane or altering the rate or kinetics of individual transporters (e.g., the time
an ion channel stays in the open versus closed state), or both

20.  the plasma membrane, with its hydrophobic
core, is an effective barrier to the movement
of virtually all biologically important
molecules into or out of the cell.
 Thus membrane transport proteins provide
the pathway that allows transport to occur
into and out of cells.
 However, the presence of a pathway is not
sufficient for transport to occur; an
appropriate driving force is also required.

21.  Diffusion
 is the process by which molecules move
spontaneously from an area of high
concentration to one of low concentration.
 Thus wherever a concentration gradient exists,
diffusion of molecules from the region of high
concentration to the region of low concentration
dissipates the gradient( the establishment of
concentration gradients for molecules requires
the expenditure of energy).
 Diffusion is a random process driven by the
thermal motion of the molecules

22.  Simple diffusion
 ■ is the only form of transport that is not
carrier mediated.
 ■ occurs down an electrochemical gradient
(“downhill”).
 ■ does not require metabolic energy and
therefore is passive.

24.  , the rate of diffusion will be faster for small
molecules than for large molecules. In addition,
diffusion rates are high at elevated
temperatures, in the presence of large
concentration gradients, and when diffusion
occurs in a low-viscosity medium. With all other
variables held constant, the rate of diffusion is
linearly related to the concentration gradient.
Fick’s equation can also be applied to the
diffusion of molecules across a barrier, such as a
lipid bilayer. When applied to the diffusion of a
molecule across a bilayer, the diffusion
coefficient (D) incorporates the properties of the
bilayer and especially the ability of the molecule
to diffuse through the bilayer

26.  Permeability
 ■ is the P in the equation for diffusion.
 ■ describes the ease with which a solute diffuses through a membrane.
 ■ depends on the characteristics of the solute and the membrane.
 a. Factors that increase permeability:
 ■ ↑ Oil/water partition coefficient of the solute increases solubility in the
lipid of the membrane.
 ■ ↓ Radius (size) of the solute increases the diffusion coefficient and
speed of diffusion.
 ■ ↓ Membrane thickness decreases the diffusion distance.
 b. Small hydrophobic solutes (e.g., O2 , CO2 ) have the highest
permeabilities in lipid membranes.
 c. Hydrophilic solutes (e.g., Na+ , K+ ) must cross cell membranes
through water-filled channels, or pores, or via transporters.
 If the solute is an ion (is charged), then its flux will depend on both the
concentration difference and the potential difference across the
membrane.

27. ■ includes :
 facilitated diffusion
 primary active transport
 secondary active transport
■ The characteristics of carrier-mediated transport are
1. Stereospecificity.
For example, d-glucose (the natural isomer) is transported by facilitated diffusion, but
the l-isomer is not.
Simple diffusion, in contrast, would not distinguish between the two isomers because it
does not involve a carrier.
2. Saturation.
The transport rate increases as the concentration of the solute increases, until
the carriers are saturated.
The transport maximum (Tm) is analogous to the maximum velocity (Vmax) in
enzyme kinetics.
3. Competition.
Structurally related solutes compete for transport sites on carrier molecules.
For example, galactose is a competitive inhibitor of glucose transport in the
small intestine.

28.  Facilitated diffusion
 a substance transported in this manner diffuses
through the membrane with the help of a
specific carrier protein.
 That is, the carrier facilitates diffusion of the
substance to the other side.

29. Characteristics of facilitated diffusion
■ occurs down an electrochemical gradient (“downhill”),
similar to simple diffusion.
■ does not require metabolic energy and therefore is passive.
■ is more rapid than simple diffusion.
■ is carrier mediated and therefore exhibits
stereospecificity, saturation, and competition.
Example of facilitated diffusion
■ Glucose transport in muscle and adipose cells is
“downhill,” is carrier-mediated, and is inhibited by sugars
such as galactose;
therefore, it is categorized as facilitated diffusion. In
diabetes mellitus, glucose uptake by muscle and adipose
cells is impaired because the carriers for facilitated
diffusion of glucose require insulin

30.  passive transport
 When the net movement of a molecule across a
membrane occurs in the direction predicted by
the electrochemical gradient
 sometimes referred to as either “downhill
transport” or “transport with the
electrochemical gradient
 Ex: the movement of glucose into the cell and
the movement of K+ out of the cell

31.  active transport
 if the net movement of a molecule across the
membrane is opposite to that predicted by the
electrochemical gradient
 a process that requires the input of energy (e.g.,
ATP).
 is sometimes referred to as either “uphill
transport” or “transport against the
electrochemical gradient.”

32.  Primary active transport
 Characteristics :
 ■ occurs against an electrochemical gradient
(“uphill”).
 ■ requires direct input of metabolic energy
in the form of adenosine triphosphate (ATP)
and therefore is active.
 ■ is carrier mediated and therefore exhibits
stereospecificity, saturation, and
competition.

33.  Examples of primary active transport
 a. Na+ , K+ -ATPase (or Na+ –K+ pump) in cell membranes
 transports Na+ from intracellular to extracellular fluid and K+ from extracellular
to intracellular fluid;
 it maintains low intracellular [Na+ ] and high intracellular [K+ ]
 Both Na+ and K+ are transported against their electrochemical gradients.
 Energy is provided from the terminal phosphate bond of ATP.
 The usual stoichiometry is 3 Na+ /2 K+
 Specific inhibitors of Na+ , K+ -ATPase are the cardiac glycoside drugs ouabain
and digitalis
 b. Ca2+ -ATPase (or Ca2+ pump)
 in the sarcoplasmic reticulum (SR) or cell membranes transports Ca2+ against an
electrochemical gradient.
 Sarcoplasmic and endoplasmic reticulum Ca2+ -ATPase is called SERCA.
 c. H+ , K+ -ATPase (or proton pump)
 in gastric parietal cells transports H+ into the lumen of the stomach against its
electrochemical gradient.
- It is inhibited by proton pump inhibitors, such as omeprazole.

34.  Secondary active transport
 The transport of two or more solutes is coupled.
 One of the solutes (usually Na+ ) is transported “downhill” and
provides energy for the “uphill” transport of the other solute(s).
 Metabolic energy is not provided directly but indirectly from the Na+
gradient that is maintained across cell membranes.
 Thus, inhibition of Na+ , K+ -ATPase will decrease transport of Na+ out
of the cell, decrease the transmembrane Na+ gradient, and eventually
inhibit secondary active transport.
 If the solutes move in the same direction across the cell membrane, it
is called cotransport or symport.
 ■ Examples are:
 Na+ -glucose cotransport in the small intestine and renal
early proximal tubule and Na+ –K+ –2Cl– cotransport
in the renal thick ascending limb.
 If the solutes move in opposite directions across the cell membranes,
it is called countertransport, exchange, or antiport.
 ■ Examples are
 Na+ -Ca2+ exchange and Na+ –H+ exchange.

36.  osmosis
 The movement of water across cell membranes
 Osmotic pressure
 is determined by the number of solute molecules
dissolved in the solution.
 It is not dependent on such factors as the size of the
molecules, their mass, or their chemical nature (e.g.,
valence).
 Osmotic pressure (π), measured in atmospheres (atm), is
calculated by
 van’t Hoff’s law as follows:
 osmotic pressure depends on the concentration of osmotically
active particle
 π = nCRT
 where n = number of dissociable particles per molecule
 C = total solute concentration
 R = gas constant
 T = temperature in degrees Kelvin

37.  The osmotic pressure increases when the solute concentration
increases.
 The higher the osmotic pressure of a solution, the greater the
water flow into it.
 Two solutions having the same effective osmotic pressure are
isotonic because no water flows across a semipermeable
membrane separating them.
 If two solutions separated by a semipermeable membrane have
different effective osmotic pressures,
 the solution with the higher effective osmotic pressure : hypertonic
 the solution with the lower effective osmotic pressure : hypotonic
 Water flows from the hypotonic to the hypertonic solution.
 Colloid osmotic pressure, or oncotic pressure, is the osmotic
pressure created by proteins (e.g., plasma proteins).

38.  Reflection coefficient (σ)
 ■ is a number between zero and one that describes the ease with which a solute
permeates a membrane.
 If the reflection coefficient is one, the solute is impermeable. Therefore, it is retained
in the original solution, it creates an osmotic pressure, and it causes water flow.
 Serum albumin (a large solute) has a reflection coefficient of nearly one.
- If the reflection coefficient is zero, the solute is completely permeable.
Therefore, it will not exert any osmotic effect, and it will not cause water
flow.
Urea (a small solute) usually has a reflection coefficient of close to zero and it is,
therefore, an ineffective osmole.
Calculating effective osmotic pressure
■ Effective osmotic pressure is the osmotic pressure (calculated by van’t Hoff’s law)
multiplied by the reflection coefficient.
■ If the reflection coefficient is one, the solute will exert maximal effective osmotic
pressure.
If the reflection coefficient is zero, the solute will exert no osmotic pressure

39.  Ion channels
 - are integral proteins that span the membrane and, when
open, permit the passage of certain ions.
 1. Ion channels are selective; they permit the passage of
some ions, but not others.
 Selectivity is based on the size of the channel and the
distribution of charges that line it.
 ■ For example, a small channel lined with negatively charged
groups will be selective for small cations and exclude large
solutes and anions. Conversely, a small channel lined with
positively charged groups will be selective for small anions and
exclude large solutes and cations.
 2. Ion channels may be open or closed.
 When the channel is open, the ion(s) for which it is selective
can flow through.
 When the channel is closed, ions cannot flow through

40.  3. The conductance of a channel depends on the probability that the
channel is open.
 The higher the probability that a channel is open, the higher the conductance, or
permeability.
 Opening and closing of channels are controlled by gates.
 a. Voltage-gated channels are opened or closed by changes in membrane
potential.
 The activation gate of the Na+ channel in nerve is opened by depolarization; when
open, the nerve membrane is permeable to Na+ (e.g., during the upstroke of the
nerve action potential).
 The inactivation gate of the Na+ channel in nerve is closed by depolarization; when
closed, the nerve membrane is impermeable to Na+ (e.g., during the repolarization
phase of the nerve action potential).
 b. Ligand-gated channels are opened or closed by hormones, second
messengers, or neurotransmitters.
 For example, the nicotinic receptor for acetylcholine (ACh) at the motor end
plate is an ion channel that opens when ACh binds to it.
 When open, it is permeable to Na+ and K+ , causing the motor end plate to
depolarize.

41. diffusion potential
 is the potential difference generated across a
membrane because of a concentration difference of
an ion.
 can be generated only if the membrane is permeable
to the ion.
 The size of the diffusion potential depends on the
size of the concentration gradient.
 The sign of the diffusion potential depends on
whether the diffusing ion is positively or negatively
charged.
 are created by the diffusion of very few ions and,
therefore, do not result in changes in concentration
of the diffusing ions.

42. equilibrium potential
 is the potential difference that would exactly balance
(oppose) the tendency for diffusion down a
concentration difference.
 At electrochemical equilibrium, the chemical and
electrical driving forces that act on an ion are equal
and opposite, and no more net diffusion of the ion
occurs.

43.  The Nernst equation
 is used to calculate the equilibrium potential at a
given concentration difference of a permeable
ion across a cell membrane.
 It tells us what potential would exactly balance
the tendency for diffusion down the
concentration gradient;
 in other words, at what potential would the ion
be at electrochemical equilibrium?

45.  action potential
 is a rapid, all-or-none change in the membrane
potential, followed by a return to the resting
membrane potential.

46.  Resting membrane potential
 is expressed as the measured potential difference across the cell membrane in millivolts (mV).
 is, by convention, expressed as the intracellular potential relative to the extracellular potential.
 Thus, a resting membrane potential of −70 mV means 70 mV, cell negative.
 The resting membrane potential is established by diffusion potentials that result from
concentration differences of permeant ions.
 Each permeable ion attempts to drive the membrane potential toward its equilibrium potential.
 Ions with the highest permeabilities, or conductances, will make the greatest contributions to the
resting membrane potential, and those with the lowest permeabilities will make little or no
contribution.
 For example, the resting membrane potential of nerve is −70 mV, which is close to the calculated
K+ equilibrium potential of −85 mV, but far from the calculated Na+ equilibrium potential of +65
mV.
 At rest, the nerve membrane is far more permeable to K+ than to Na+ .
 The Na+ –K+ pump contributes only indirectly to the resting membrane potential by maintaining,
across the cell membrane, the Na+ and K+ concentration gradients that then produce diffusion
potentials.
 The direct electrogenic contribution of the pump (3 Na+ pumped out of the cell for every 2 K+
pumped into the cell) is small.

48. Driving force and current flow
■ The driving force on an ion is the difference between
the actual membrane potential (Em) and the ion’s
equilibrium potential (calculated with the Nernst
equation).
■ Current flow occurs if there is a driving force on the
ion and the membrane is permeable to the ion.
The direction of current flow is in the same direction as
the driving force.
The magnitude of current flow is determined by the
size of the driving force and the permeability (or
conductance) of the ion.
If there is no driving force on the ion, no current flow
can occur.
If the membrane is impermeable to the ion, no current
flow can occur

49.  a. Depolarization
 makes the membrane potential less negative (the cell
interior becomes less negative).
b. Hyperpolarization
-makes the membrane potential more negative (the cell
interior becomes more negative).
c. Inward current
is the flow of positive charge into the cell.
Inward current depolarizes the membrane potential.
d. Outward current
is the flow of positive charge out of the cell.
Outward current hyperpolarizes the membrane
potential.

50. • e. Action potential
 is a property of excitable cells (i.e., nerve, muscle) that
consists of a rapid depolarization, or upstroke, followed
by repolarization of the membrane potential.
 Action potentials have stereotypical size and shape, are
propagating, and are all-or-none.
f. Threshold
is the membrane potential at which the action potential
is inevitable.
At threshold potential, net inward current becomes
larger than net outward current.
The resulting depolarization becomes self-sustaining and
gives rise to the upstroke of the action potential.
If net inward current is less than net outward current, no
action potential will occur (i.e., all-or-none response).

51.  Nerve signals are transmitted by action
potentials, which are rapid changes in the
membrane potential that spread rapidly
along the nerve fiber membrane.
 Each action potential begins with a sudden
change from the normal resting negative
membrane potential to a positive potential
and ends with an almost equally rapid
change back to the negative potential.
 To conduct a nerve signal, the action
potential moves along the nerve fiber until it
comes to the fiber’s end.

52.  The successive stages of the action potential are
as follows:
1. Resting Stage.
 The resting stage is the resting membrane
potential before the action potential begins.
 The membrane is said to be “polarized” during
this stage because of the −70 millivolts negative
membrane potential that is present
 It is the result of the high resting conductance to
K+ , which drives the membrane potential
toward the K+ equilibrium potential.
 At rest, the Na+ channels are closed and Na+
conductance is low

53. DEPOLARIZATION STAGE
 At this time, the membrane suddenly
becomes permeable to sodium ions, allowing
rapid diffusion of positively charged sodium
ions to the interior of the axon.
 The normal polarized state of −70 millivolts
is immediately neutralized by the inflowing,
positively charged sodium ions, with the
potential rising rapidly in the positive
direction

54. 1) Inward current depolarizes the membrane potential to threshold.
2) Depolarization causes rapid opening of the activation gates of the
Na+ channels, and the Na+ conductance of the membrane
promptly increases.
3) The Na+ conductance becomes higher than the K+ conductance,
and the membrane potential is driven toward (but does not quite
reach) the Na+ equilibrium potential of +65 mV.
Thus, the rapid depolarization during the upstroke is caused by an
inward Na+ current.
(4) The overshoot is the brief portion at the peak of the action
potential when the membrane potential is positive.
(5) Tetrodotoxin (TTX) and lidocaine block these voltage-sensitive
Na+ channels and abolish action potentials

55.  Within a few 10,000ths of a second after the
membrane becomes highly permeable to
sodium ions, the sodium channels begin to
close, and the potassium channels open to a
greater degree than normal.
 Then, rapid diffusion of potassium ions to the
exterior reestablishes the normal negative
resting membrane potential

56.  (1) Depolarization also closes the inactivation gates of the Na+ channels
(but more slowly than it opens the activation gates).
 Closure of the inactivation gates results in closure of the Na+ channels,
and the Na+ conductance returns toward zero.
 (2) Depolarization slowly opens K+ channels and increases K+
conductance to even higher levels than at rest.
 Tetraethylammonium (TEA) blocks these voltage-gated K+ channels.
 (3) The combined effect of closing the Na+ channels and greater opening
of the K+ channels makes the K+ conductance higher than the Na+
conductance, and the membrane potential is repolarized.
 Thus, repolarization is caused by an outward K+ current.

58.  Undershoot (hyperpolarizing afterpotential)
 ■ The K+ conductance remains higher than
at rest for some time after closure of the
Na+ channels.
 During this period, the membrane potential
is driven very close to the K+ equilibrium
potential.

59.  When a cell is refractory, it is either
completely unable to fire an action potential
or it requires a much stronger stimulation
than usual.
 During much of the action potential, the cell
is completely refractory because it will not
fire another action potential no matter how
strongly it is stimulated.

60. absolute refractory period
 occurs when a large fraction of the Na+
channels are inactivated and therefore
cannot be reopened until the membrane is
repolarized.
 During this period, the critical number of Na+
channels required to produce an action
potential cannot be recruited

61.  Absolute refractory period
 ■ is the period during which another action
potential cannot be elicited, no matter how
large the stimulus.
 ■ coincides with almost the entire duration of
the action potential.
 Explanation: Recall that the inactivation gates
of the Na+ channels are closed when the
membrane potential is depolarized. They remain
closed until repolarization occurs. No action
potential can occur until the inactivation gates
open.

62.  During the latter part of the action potential,
and during the afterhyperpolarization period,
the cell is able to fire a second action
potential, but a stimulus stronger than
normal is required. This period is called the
relative refractory period.

63.  Relative refractory period
 ■ begins at the end of the absolute refractory
period and continues until the membrane
potential returns to the resting level.
 ■ An action potential can be elicited during this
period only if a larger than usual inward current
is provided.
 ■ Explanation: The K+ conductance is higher
than at rest, and the membrane potential is
closer to the K+ equilibrium potential and,
therefore, farther from threshold; more inward
current is required to bring the membrane to
threshold.

64.  When a nerve is depolarized very slowly, the normal
threshold may be passed without the firing of an
action potential
 occurs when the cell membrane is held at a
depolarized level such that the threshold potential is
passed without firing an action potential.
 occurs because depolarization closes inactivation
gates on the Na+ channels.
 is demonstrated in hyperkalemia, in which skeletal
muscle membranes are depolarized by the high serum
K+ concentration.
 Although the membrane potential is closer to
threshold, action potentials do not occur because
inactivation gates on Na+ channels are closed by
depolarization, causing muscle weakness.

65.  Fundamental to nervous system function is
the transmission of information along
neuronal pathways.
 To accomplish this, neurons generate action
potentials that propagate down the length of
their axon without decrement in size in order
to trigger neurotransmitter release from the
presynaptic term

66.  Propagation of action potentials
 ■ occurs by the spread of local currents to adjacent areas
of membrane, which are then depolarized to threshold and
generate action potentials
 Conduction velocity is increased by:
 a. ↑ fiber size.
 Increasing the diameter of a nerve fiber results in
decreased internal resistance; thus, conduction velocity
down the nerve is faster.
 b. Myelination.
 Myelin acts as an insulator around nerve axons and
increases conduction velocity.
 Myelinated nerves exhibit saltatory conduction because
action potentials can be generated only at the nodes of
Ranvier, where there are gaps in the myelin sheath

67.  Direction of Propagation.
 an excitable membrane has no single
direction of propagation, but the action
potential travels in all directions away from
the stimulus—even along all branches of a
nerve fiber—until the entire membrane has
become depolarized.

68.  Once an action potential has been elicited at any point on
the membrane of a normal fiber, the depolarization
process travels over the entire membrane if conditions are
right, but it does not travel at all if conditions are not
right.

 it applies to all normal excitable tissues.
 Occasionally, the action potential reaches a point on the
membrane at which it does not generate sufficient voltage
to stimulate the next area of the membrane.
 When this situation occurs, the spread of depolarization
stops.
 Therefore, for continued propagation of an impulse to
occur, the ratio of action potential to threshold for
excitation must at all times be greater than 1.
 This “greater than 1” requirement is called the safety
factor for propagation

69.  PLATEAU IN SOME ACTION POTENTIALS
 In some cases, the excited membrane does
not repolarize immediately after
depolarization; instead, the potential
remains on a plateau near the peak of the
spike potential for many milliseconds before
repolarization begin

70.  the plateau greatly prolongs the period of depolarization.
 This type of action potential occurs in heart muscle fibers, where
the plateau lasts for as long as 0.2 to 0.3 second and causes
contraction of heart muscle to last for this same long period.
 The cause of the plateau is a combination of several factors.
 First, in heart muscle, two types of channels contribute to the
depolarization process:
 (1) the usual voltage-activated sodium channels, called fast channels;
and
 (2) voltageactivated calcium-sodium channels (L-type calcium
channels), which are slow to open and therefore are called slow
channels.
 Opening of fast channels causes the spike portion of the action
potential, whereas the prolonged opening of the slow calcium-sodium
channels mainly allows calcium ions to enter the fiber, which is largely
responsible for the plateau portion of the action potential.

72.  1. Ion channels are integral membrane proteins that have
ion-selective pores.
 An ion channel typically has two states: high conductance
(open) and zero conductance (closed).
 Different regions of an ion channel protein act as gates to
open and close the channel.
 The channel flips spontaneously between the open and
closed states.
 2. For a voltage-dependent channel, the fraction of time
that the channel spends in the open state is a function of
the transmembrane potential difference.
 3. The action potential is generated by the rapid opening
and subsequent voltage inactivation of voltage-dependent
Na+ channels and by the delayed opening and closing of
voltage-dependent K+ channels.

73.  4. The absolute and relative refractory
periods result from voltage inactivation of
Na+ channels and the delayed closure of K+
channels in response to membrane
repolarization. These refractory periods limit
the firing rate of action potentials.
 5. Subthreshold signals and action potentials
are conducted along the length of a cell by
local circuit currents.
 Subthreshold signals are conducted only
electrotonically, and thus decrease with
distance.

74.  6. The action potential is propagated rather than merely
conducted; it is regenerated as it moves along the axon. In
this way, an action potential retains the same size and
shape as it travels along the axon.
 7. A large-diameter axon has greater propagation velocity
because increased axon diameter lowers axial resistance
and allows greater amounts of current to flow farther
down the axon.
 8. Myelination dramatically increases the conduction
velocity of a nerve axon because myelin increases
membrane resistance and lowers membrane capacitance.
 Myelination allows an action potential to be conducted
very rapidly from one node of Ranvier to the next. This
makes the action potential appear to jump from node to
node in a form of conduction called saltatory conduction

75.  9. A receptor responds preferentially to a
particular form of stimulus energy. Its
receptive field is that part of a sensory
domain in which energy can affect the
receptor.
 10. Receptor potentials are the result of
transduction of sensory stimuli. These
potentials reflect the specific parameters of
the stimulus and, if they exceed threshold,
alter the action potential firing patterns of
the afferent neurons