Physiology Bio2424
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Ch 8
Excitable cells
- nerve & muscle cells can generate & propagate electrical signals
- all cells able to establish RMP (resting membrane potential)
Law of Conservation of Electric Charge states that the net amount of electric charge produced in any process is zero.
This means that for very positive charge on an ion, there is an electron on another ion. Overall the human body is
electrically neutral.
- Work must be performed to separate charges. However, after separation, the electrical force can be harnessed when
the charges are allowed to come together again. Separated charges have potential energy.
- If separated positive & negative charges can move freely toward each other, the material through which they are moving
is called a conductor (e.g., water). But if separated charges are unable to move through the material that separates
them the material is known as an insulator (e.g., phospholipid bilayer).
- Flashlights shine (work) when you flick the switch on (this completes a circuit) and electrons flow from a negatively
charge area to a positively charged area. Electrons keep flowing until there is equilibrium. The measure of the potential
energy is called voltage; V = electrical potential. In biological circuits, we’re usually concerned with its potential to do
work. For the low potential energy stored in human systems, we use millivolts: 1mV = 0.001V.
- In the body electrical events occur in an aqueous medium & electrical currents are induced due to the flow of ions rather
than electrons.
depolarization = difference between inside & outside (potential difference) decreases; potential becomes more (+);
depolarization across the plasmalemma induces a voltage change from -70mV to +30mV
hyperpolarization = potential difference increases; measured potential becomes more negative (to -90mV), so it’s more
difficult to depolarize (start an action potential); hyperpolarization “freezes” a nerve’s fx
repolarization = return to normal membrane potential from either direction
overshoot = portion of the action potential that goes above 0mV
Ion Movement across the cell membrane creates electrical signals, aka Action Potentials
1. Na+ influx depolarizes cell
2. K+ efflux repolarizes cell
3. release of neurotransmitter
4. Ca+2 influx triggers exocytosis of neurotransmitter
5. Inhibition: Cl- influx hyperpolarizes the cell
Relatively very few ions are required to change the membrane potential: depolarize or hyperpolarize it—the
concentration gradient is virtually unaffected!
How do ions get across plasmalemma?
Gated Ion Channels
mechanically gated = open in response to physical forces (pressure, light)
chemically gated = open in response to ligand binding (acetylcholine)
voltage gated = open in response to depolarization
K+ channels are voltage gated, open in response to depolarization
Na+ channels are double gated and voltage regulated
Ca+2 channels (at axon terminal) are voltage gated, open in response to depolarization
Cl- channels are chemically gated, open in response to a ligand binding to a protein channel receptor site
also, leak channels are ion channels that are usually open
Graded Potentials
Depolarization (opening Na+ channels) or hyperpolarization (opening K+, or Cl- channels) occurring in dendrites or cell
body
amplitude reflects stimulus intensity
depolarization wave = local current flow
graded potential travels through neuron until reach trigger zone region
Threshold at -55mV
1. graded potentials reaching threshold @ trigger zone initiate AP
2. threshold not reached, graded potential dies out, no AP produced
3. summation of graded potentials can occur
spatial: adding simultaneous graded potentials occurring @ different locations
temporal: two sequential subthreshold stimuli can be summed if close enough in time
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What happens at threshold that causes an action potential?
Opening of voltage gated Na+ channels!! —the influx of Na+ induces a local electric current
Action Potentials
- identical to one another
- don't diminish as move down axon
- all or none principal (on or off)
- frequency of AP's reflects stimulus intensity—as opposed to graded where the amplitude (size) reflects stimulus
intensity; the signal strength is the same, so their frequency is increased to indicate a stronger stimulus (flick the lights
on & off faster—“Danger Will Robinson! Danger!”)
Action Potential 3 Phases
AP Depolarization: Na influx followed by K efflux
1. Rising Action Potential
Due to temporary increase in Na+ permeability (Na+ rushes into cell): depolarization  voltage gated Na+ channels
open  Na+ flows into ICF, further depolarization  membrane potential reaches 0 mV  Na+ no longer driven in
by electrical potential (no negative charge to attract the positive Na +), but movement continues because of higher
Na concentration in ECF  voltage gated Na+ channels close (second Na+ gate closure delayed by 0.5msec
seconds after initial depolarization)  AP peaks +30 mV (equilibrium reached at +60mV, but Na+ channels close
“too soon”)
2. Falling phase
primarily due to increase in K+ permeability (out of cell): Voltage gated K+ channels open at +30mV (K+ gates
slower to open, so peak K+ activity past peak Na+)  K+ moves into ECF down electrochemical gradient (more K+ in
cell & charge at +30mV, so potassium diffuses out)  K+ efflux drives membrane potential difference more
negative, toward resting potential  membrane potential hyperpolarized as K+ channels close, heading toward -90
mV
3. After-hyperpolarization (undershoot)
Due to extra K+ efflux: gated K+ channels close  permeability returns to resting membrane levels 
K+ redistributes slightly, leaking into cell, bringing resting membrane potential to -70 mV
- ligand gated Na+ channels open
- voltage gated Na+ channels open -55 mV
- voltage gated Na+ channels close +30 mV
- voltage gated K+ channels open
Refractory Period = time after first AP when impossible or difficult to initiate second AP; keeps signal transmission
direction one-way
absolute: Na+ channels closed, K+ open, no Na+ movement, prevents summation of AP's, limits speed of AP
transmission
relative: Na+ channels reset, K+ channels still open, stronger than normal depolarizing stimulus required for AP
Graded potentials are variable strength signals that dissipate quickly (travel short distances); they’re proportional to the
stimulus, i.e., more neurotransmitters binding, more ions influxing, so greater depolarization occurs (stronger electric
currents are formed).
Action potentials are large, uniform plasmalemma depolarizations (100mV change, from –70 to +30mV) that can travel
rapidly for long distances (can insure signal transmission from hallux to lumbar plexus).
Na+/K+ ATPase pump
- no direct role in generating the Action Potential itself: fx to establish overall concentration gradient, the RMP
- very few ions moved overall & ion concentration relatively unchanged, so gradient easily reset for rapid successional
firing of AP's
- if poisoned, can continue firing AP's for a short time
Conduction of AP: one AP is exactly like another
- movement of AP along axon @ high speed
- forward flow only—refractory period prevents “backfiring”
- sequential opening of voltage gated Na+ channels
- same sequence of events as w/initial AP: a chain rx of depolarization cascades down the axon like a line of dominos;
an AP is positive feedback loops traveling down the axon
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Graded Potential
Signal type
where initiated
gated channel types
ions involved
signal type
Action Potential
input signal
conduction signal
usu. dendrites & cell body
axon hillock (trigger zone)
mechanical, chemical, or voltage-gated
voltage-gated
usu. Na+, Ca+, Cl-
Na+ & K+
depolarizing or hyperpolarizing
depolarizing
depends on stimulus; can be summed
constant; absolute refractory period (can’t be summed)
cause of initiation
ion influx through channels
above threshold graded potential reaches axon hillock
unique characters
no minimum level required to initiate; summation
threshold stimulus required; stimulus
strength indicated by signal frequency
signal strength
current = flow of positive charges to negative charges (opposite charges attract); the inner plasmalemma fluid is
negatively charged compared to the outer plasmalemma fluid, so when Na enters the axon, an electrical current
is induced across the plasmalemma
Events at End of Axon
voltage gated Ca+2 channels open, due to depolarization wave  Ca+2 influx into cell  triggers exocytosis of vesicles
containing neurotransmitters  neurotransmitters released across the synapse to target
If most organelles are located in nerve cell body, how do neurotransmitter-containing vesicles end up far, far away at
axon terminal? axonal transport: microtubule movement of vesicles.
How much ATP does axonal transport cost?
MEMBRANE POTENTIALS/CHARACTERISTICS
1. All cell membranes have a membrane potential, which is a separation of electrical charges across the membrane on
the inside and outside or a difference in the # of cations to anions in the ECF & ICF.
2. These potentials are characterized by a slight excess of negative charges that line up along the inside the cell
membrane and are separated from the slight excess of positive charges lined up on the outside of the plasmalemma.
(Inside is negatively charged with respect to the outside). Positive charges are attracted to negative charges (i.e.,
opposites attract, likes repel).
3. However, these (+) & (-) charges are not equally distributed across the membrane.
4. This separation of opposite charges is generated and maintained by a balanced interplay between active & passive
forces, as well as by differential permeability of Na+, K+, & the intracellular protein anions.
5. In the body, these electrical charges are not carried by electrons (there are no free electrons in the body), but rather by
ions and charged molecules. Remember ions are positive or negative atoms due to the gain or loss of electrons. A
positive ion or cation lost at least one electron, so that the atom has a net positive charge. These are called cations.
A negative ion or anion gained at least one electron, so that the atom has a net negative charge.
3 Major Ion Concentrations that are Responsible for Membrane Potentials:
Na+
K+
“A-“ (protein)
ion/molecule ECF (in mM/L)
150
5
0
ICF
15
150
65
Relative Permeability
1
50-75
0
Generalities of the Ions
1. The ions responsible are Na+, K+, and large negatively charged intracellular proteins ( = A-) that are assembled by
protein synthesis inside the cell and are too large to leave.
2. There is 15x more Na+ in the ECF than in the ICF.
3. There is 30x more K+ in the ICF than in the ECF.
4. K+ is much more permeable than either Na+ or A-.
5. Other ions in the ECF contribute to its net charge, primarily Cl-.
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How is the Distribution Maintained?
1. Sodium/potassium ATPase maintains the concentration gradients in an RMP of Na + & K+ in the ECF & ICF—the “boat
is leaky.”
- How many Na+'s are pumped out & how many K+'s pumped in for each transport?
- There are more positive charges on the outside of the plasmalemma than the inside, and there’s not enough K +'s to
balance out the negative proteins on the inside.
- K+ tends to leak out of the cell, since there is a [ high ] on the inside (ICF) and a [ low ] outside (ECF).
- Na+ tends to diffuse into the cell, since there is a [ high ] on the outside (ECF) and a [ low ] inside (ICF).
- Both Na+ & K+ can diffuse across (passively cross) the plasmalemma through protein channels specific for each of
them. It is usually much easier for K+ than Na+ to get through the membrane because typically more K+ channels
than Na+ channels are open. In a typical nerve cell that is at rest (not conducting impulses), the membrane is
about 50-75 times more permeable to K+ than Na+.
Resting Membrane Potential
1. RMP's are due to the ionic flow of Na+ & K+ across the plasmalemma, the inside of the membrane is negatively
charged with respect to the outside.
2. The voltage established across the membrane by the distribution of Na + & K+ is about -70mV.
- The minus sign reflects that fact that the inside is relatively negatively charged with respect to the outside.
- This potential difference at rest is called the resting membrane potential, which equals the charge difference that
exists when an excitable cell is not displaying an electrical signal.
- All cells of the body exhibit a resting membrane potential, but values vary from -40mV to -90mV.
3. The resting membrane potential reflects the properties of the different protein channels in the membrane.
- Potassium ions diffuse out of the cell along their concentration gradient much more easily and quickly than sodium
ions can enter the cell along their protein channels.
- As potassium starts to leak out of the cell, the outside become more positive than the inside, and any stray
negatively charged particles (anions) will tend to be drawn toward the inner side of the membrane (opposites
attract).
- The inner side of the membrane is now more negatively charged with respect to the outside, because there are
negatively charged particles clinging to the inside of the membrane, and because you have a slight increase in
the number of positively charged ions on the outside of the membrane, as some of the potassium has diffused
out.
- There is a little less than 1/10th of a volt difference between the outside & inside, or more correctly,
-70mV = resting membrane potential.
4. You would expect that the concentrations of Na & K would flow until they reached equilibrium (diffusion), but they
never reach equilibrium, because the Na/K pump counteracts the leakage of Na+ into the cell & K+ out of the
cell.
- Remember, for every 3 Na+’s pumped outside to the ECF, there are 2 K+'s pumped inside to the ICF.
- Thus, the Na/K pump stabilizes the resting membrane potential by maintaining the electrochemical gradients for
sodium & potassium.
What's in a name? Resting Membrane Potential Difference, aka Polarized Plasmalemma
1. The resting part of the name comes from the fact that this electrical gradient is seen in all living cells, even those that
appear to be without electrical activity.
2. The potential part of the name come from the fact that the electrical gradient created by the active transport of ions
across the cell membrane is a source of stored energy, just as the concentration gradient is a form of potential
energy.
- When oppositely charged molecules come back together, they release energy that can be used to do work in a
similar fashion that molecules moving down their concentration gradient can perform work.
- The work done by electrical energy includes opening voltage-gated membrane channels and sending electrical
signals along the plasmalemma of nerve cells & sarcolemma of muscle cells.
3. The difference part of the name is to remind you that the membrane potential represents a difference in the electrical
charge inside & outside the cell. The word difference is often dropped.
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Membrane Potentials That Act as Signals
All cells posses membrane potential, but 2 types of cells have a specialized use for the potential. These are called
excitable cells.
- They produce electrochemical signals when excited & undergo fluctuations in membrane potential.
- Neuron & muscle cells use changes in membrane potential as signals for receiving, integrating, & sending information
A change in the resting membrane potential can be produced by
1. Anything that changes membrane permeability to any type of ion
OR
2. Anything that alters ion concentrations on the two sides of the membrane.
Stimuli affect the resting membrane potential (polarized)
1. If there is no stimulus the membrane is said to be polarized: the membrane has potential; there is a separation of
charges or a voltage across the plasmalemma.
2. If the membrane potential becomes more positive in response to stimuli, it is said to be depolarized, i.e., going from 70mV to -55mV or to +30mV
3. If the membrane potential moves, becomes more negative in response to stimuli, it is said to be hyperpolarized.
4. Repolarization: the membrane returns to its resting potential, after having been depolarized by a stimulus.
The Amount of Change in the Potential is Proportional to the Strength of Stimulus up to a Point.
The larger the stimulus, the more the RMP will change
- A small stimulus: -70mV to -60mV (depolarizes); -70mV to -80mV (hyperpolarizes)
- A large stimulus: -70mV to -55mV (depolarizes)
or lots of small stimuli applied very quickly -70mV to -90mV (hyperpolarizes)
- These are considered graded potentials until a membrane potential reaches -55mV. Above this threshold value it is
called an action potential.
There are 2 Basic Forms of Electrochemical Signals: Graded Potentials & Action Potentials
1. Graded Potentials are short-lived local changes in membrane potential that occur in varying degrees of magnitude:
-70 to -60mV or -70 to -65 mV.
a) These changes cause local flow of current that decrease with distance traveled.
b) Graded potentials are called "graded" because their magnitude varies directly with the intensity of the
stimulus. The more intense the stimulus, the more the voltage changes & the farther the current flows.
c) However, most of the charge is quickly lost through the membrane as it travels (decreases as it moves), and the
current dies out within a few mm of the original site.
d) Example, light stimulating specialized nerve cells in the eye, and interaction with a chemical messenger with a
surface receptor on a nerve, muscle, or membrane.
e) Not useful for long distances, but graded potentials are what initiate action potentials, which are the long-distance
signals.
2. Action Potentials are the general means of communication in nerve & muscles cells. The information carried in the
signals can be transported over large distances.
They are characterized by brief rapid reversal of the membrane potential. The inside becomes positive with
respect to the outside, and an electrical signal is able to spread throughout the membrane at a constant level.
AP’s do not have a decreasing signal strength over distance, as in graded potentials.
ACTION POTENTIALS
To initiate an action potential, a triggering (sensory receptor, etc.) event causes the membrane to depolarize.
- Many stimuli can cause depolarization: heat, light, pressure, chemicals, vibration, sound, etc.
- Depolarization proceeds slowly at first until it reaches a critical level known as the threshold potential,
-70mV to -55mV, then the depolarization process becomes self-generating.
Once the Threshold Potential is Reached:
1. Na channels open & Na ions rush inward and the membrane becomes less negative (reversal of potential) to about
+30mV. The explosively rising phase of the AP (period of sodium permeability) persists for only about 1ms and is
self-limiting.
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2. As the inner membrane becomes more positive, the positive intracellular charge resists further sodium entry (like
charges repel). In addition, the Na gates close after a few milliseconds of depolarization (double voltage gated), and
the membrane becomes increasingly impermeable to Na.
3. As Na entry declines, K gates open, and K rushes out of the cell more rapidly than usual, following its electrochemical
gradient. As K leaves the cell, the cell interior becomes progressively less positive, and outside becomes more
positive. So, the membrane potential moves back toward the resting level or -70mV, and the membrane is
repolarized. Repolarization continues until the inside is back to -70mV, but the pumps don't slow down right away.
They overshoot a little or hyperpolarize below -70mV, and the voltage then settles back up to -70mV.
4. Na/K pumps then restore ionic distributions. Only small amounts of Na + & K+ are exchanged, and since an axonal
membrane has thousands of Na/K pumps, these small ionic depolarization movements are quickly reset.
Propagation of an Action Potential
When an AP occurs at one point in a nerve cell membrane, it causes an electric current to flow to adjacent portions of the
membrane, which stimulate the rest of the membrane to threshold, and the AP spreads. Neurotransmitters, at the
dendrites, signal a graded potential. If the graded potential crosses threshold, then an action potential is induced down
the axon to the telodendria, which then release neurotransmitter to the next nerve’s dendrites.
- Depolarization & repolarization are very rapid series of events (1/1000th of a sec = 1 msec).
- If the generated AP is to serve as the neuron's signaling device, it must be propagated (sent or transmitted) along the
axon's entire length to the telodendria.
1. AP's are generated by the inward movement of Na through its gates at the point of the stimulus, which is usually the
axon hillock. The inside of the membrane becomes more positive, while the outside becomes more negative =
polarity reversal.
2. Now the gates at the original site snap shut, and the Na/K pumps in the vicinity of the original stimulus kick in and
start pumping ions back against the concentration gradient = repolarization. Inactivation of Na+ channels &
activation of K+ channels.
3. The effect of having these pumps kicking in and the gates shutting down causes the same thing to happen to the
neighboring pumps & gates = local currents (Na moves in then out). In the gates "next door" the same thing
occurs, so what happens is that these local current flows depolarize & repolarize adjacent membrane areas in the
forward direction away from the origin of the action potential/nerve impulse.
4. Since the area in the opposite direction has just generated an action potential, the Na gates are closed, so no new
action potential is generated there. Thus, the impulse always propagates away from its point of origin.
5. Once initiated, an action potential is a self-propagating event that continues along the axon at a constant velocity,
producing a "domino effect."
Threshold and the All-or-None Phenomenon
1. Not all stimuli (local depolarization events) produce action potentials. The depolarization must reach threshold values
if an axon is to fire. Around 15 to 20 mV from the resting value (-55mV).
2. The action potential is initiated anytime the threshold potential is reached.
3. The action potential is an all-or-none phenomenon. It either happens completely or it doesn't happen at all. If the
stimulus doesn't depolarize the membrane to threshold level, NO AP's are generated.
- Action potentials are always the same strength/magnitude no matter how strong the stimulus strength. How can
the CNS determine whether a stimulus is intense or weak?—info it needs to make an appropriate response.
- Stimulus intensity is coded for by the number of impulses generated per second, that is, by the frequency of
impulse transmission, rather than by increases in the strength (amplitude) of the AP. The amplitude is
constant in AP’s. It differs in graded potentials.
“An AP can’t yell louder—only talk faster” to produce a stronger signal.
A graded potential can summate: “Many voices talking can create a louder voice” to produce a stronger signal.
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4. The threshold value is that membrane potential at which the outward current carried by K + is exactly equal to the
inward current created by Na+. Threshold is typically reached when the membrane has been depolarized
by 15-20mV from the resting value.
- If extra Na ions enter, further depolarization occurs, opening more Na gates and allowing more Na + entry into the
cell.
- If on the other hand, K+ leaves, the membrane potential is driven away from threshold, Na+ gates are closed, and
K+ ions continue to diffuse outward until the potential returns to its resting value.
- Compare the generation of the AP to lighting a match under a small dry twig. The searing of part of the twig can
be compared to the change in membrane permeability that initially allows more Na+ ions to enter the cell. When
that part of the twig becomes hot enough (when enough Na+ ions have entered the cell), the critical flash point
(threshold) is reached, and the flame will consume the entire twig, even if you blow out the match (the AP will be
generated and propagated regardless of whether the stimulus continues). But if the match is extinguished just
before the twig has reached the critical temp, ignition will not take place. Likewise, if too few Na + ions enter the
cell to achieve threshold, no action potential occurs.
Action potentials are usually initiated at the axon hillock because it has the lowest threshold. RMP is not uniform
throughout the postsynaptic neuron. The axon hillock has a lower threshold because it has an abundance of Na+ gates,
making it considerably more sensitive to changes in potential than the remainder of the cell body & its dendrites.
Refractory Periods
1. When a patch of neuron membrane is generating an AP, and its Na+ gates are open, the neuron is incapable
of responding to another stimulus, no matter how strong = absolute refractory period.
- It ensures that each AP is a separate, all-or-none event. Keep in mind that once an AP is generated, the Na
gates are kept open by Na+ ion currents, not by the stimulus.
- Lasts 2.5msec (1/2500th sec).
2. The interval following the absolute refractory period, when the Na gates are closed, the K gates are open, and
repolarization is occurring, is the relative refractory period.
- A threshold stimulus is unable to trigger an AP during this time, but an exceptionally strong stimulus can reopen
the Na+ gates and allow another impulse to be generated.
- Thus, by intruding into the relative refractory period, strong stimuli cause AP's to be generated more frequently.
- They also insure one-way directional flow since the Na gates are shut and cannot be opened until the region is out
of its absolute refractory period.
3. The refractory periods limit the rate at which nerve impulses can be conducted (1msec).
Absolute refractory period of neurons = 1msec, skeletal M = 10msec, & cardiac M = 300msec.
IMPULSE CONDUCTION VELOCITIES
1. Propagation of impulses by an axon is influenced by its membrane potential and by the threshold of the neuron.
2. Conduction velocities vary by a factor of 100.
- Fibers that transmit impulses most rapidly up to 130m/s (290mi/hr) are found in neural pathways where speed is
essential, such as those that mediate some postural reflexes.
- More slowly conducting axons most often serve internal organs (GI tract, glands, blood vessels), where slower
responses are not usually a handicap.
3. Impulse conduction rate depends largely on 2 structural factors: axon diameter & degree of myelination.
Influence of Axon Diameter on Velocity
1. As a general rule, the larger the axon's diameter, the faster it conducts impulses. This is because larger axons
have a greater cross-sectional and membrane surface area, which together provide easier conduction (lower
resistance), and a larger pathway for current flow, permitting adjacent membrane areas to be depolarized more
quickly.
Influence of Myelin on Impulse Conduction
Remember myelin is a whitish-yellowish, fatty layer; it’s the plasmalemma (phospholipid bilayer) of Schwann cells that
extends & wraps around the axons in neurons in the PNS. Oligodendrocyte neuroglia are responsible for myelination in
the CNS.
- Myelin serves as an insulator/resistor & prevents flow of ions.
- As a general rule, the most urgent types of info are transmitted via myelinated fibers, whereas the nervous pathways
carrying less urgent info are unmyelinated.
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1. Unmyelinated axons conduct impulses over their entire membrane surface. AP's are generated at sites immediately
adjacent to each other and conduction is relatively slow. (Thousands of ponies along the Pony Express route—
inefficient.)
2. Myelinated axons are covered by a segmented sheath of myelin, which greatly increase the rate of impulse
propagation. Electrically insulates & prevents ion leakage.
- Current can pass through the membrane of a myelinated axon only at the nodes of Ranvier, where the myelin
sheath is interrupted, and the axon is bare. Practically all active Na channels are at the nodes.
- Consequently, when an AP is generated in a myelinated axon, the local depolarization does not spread and
dissipate through the adjacent (next door) membrane, but is instead forced to move to the next node, where it
triggers another action potential = saltatory conduction, because the signal jumps from node to node along the
axon. (A dozen ponies make the trip, so there’s less starts & stops—much more efficient signal transmission.)
There are a number of demyelination diseases. Multiple sclerosis is the most common. What would you predict are some
symptoms? What causes these types of diseases?
What happens to an AP once it reaches the end of an axon?
1. The operation of the nervous system depends on the flow of information through elaborate "circuits" consisting of
chains of neurons functionally connected by synapses.
- Reflex Arc general pathway: sensory receptor, sensory neuron, interneuron (integrating center), motor
neuron, & effector.
- Information is carried via neurons by action potentials. What happens when an AP reaches the end? Remember
there is only a one-way flow of info from the receptors to CNS or CNS to effectors.
2. The neuron terminates on a:
- muscle = neuromuscular junction
- gland = neuroglandular junction
- nerve = synapse, junction between 2 communicating neurons that mediates transfer of info from one neuron to the
next or to an effector cell.
- neuron cell body (axosomatic)
- dendrites (axodendritic) = all are types of synapses
- axon (axoaxonic)
How does the impulse reach these areas?
3. At the end of the axon are telodendria and at the end of the telodendria are axon terminals with synaptic bulbs.
4. At the end of the synaptic bulb/knob is a unique junction that mediates the transfer of information from one neuron to
the next or from a neuron to an effector cell called a synapse (= to clasp or join, Greek)
- The neuron conducting impulses toward the synapse is called the presynaptic neuron (info senders). The
neuron that transmits info away from the synapse is called the postsynaptic neuron.
5. For an impulse to continue its journey it must cross the synapse
- The AP cannot cross the synaptic cleft, so as soon as the impulse or wave hits the synaptic bulb, the voltage
gated Ca+2 channels open, and Ca+2 binds to regulatory proteins that signal the synaptic vesicles in the
presynaptic neuron to undergo exocytosis, releasing their neurotransmitters into the synaptic cleft. These
neurotransmitters bind to receptor sites on the postsynaptic neuron and initiate graded potentials in the next
neuron or signal a response from an effector (e.g., muscle, gland).
Neurotransmitters: types of paracrines
1. There are over 200 types
- Acetylcholine (Ach) stimulates skeletal muscle contraction at the myoneural junction and is used by most
of the ANS: the parasympathetic Nn & the preganglionic Nn of the sympathetic system. The
postganglionic Nn of the sympathetic system use norepinephrine (Ne, an amine). The CNS also uses
Ach.
- Others: epinephrine, dopamine, serotonin, enkephalins & endorphins (opiods, “no pain”), histamines, & GABA
- structural types: acetylcholine, amino acids, amine groups, polypeptides, purines, gases, or lipids.
2. Neurotransmitters are synthesized in the neuron and stored in synaptic vesicles in the synaptic bulbs.
- Ach releasing axons & their binding sites are called cholinergic (short for acetylcholinergic). The two major types of
cholinergic receptors are muscarinic & nicotinic.
- Most sympathetic postganglionic axons release Ne and the receptors are adrenergic (“epinephrine = adrenaline”).
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Information Transfer
1. When an impulse reaches the synaptic bulb, this causes an increase in the membrane permeability to Ca.
Depolarization causes the voltage-gated Ca channels to open and Ca diffuses into the axon terminal.
2. Ca+2 signals synaptic vesicles to fuse with the membrane and release their neurotransmitter into the synaptic cleft by
exocytosis.
- Ca+2 activates a regulatory protein within the cytoplasm of the axon terminal called calmodulin, which in turn
activates an enzyme called protein kinase. This enzyme adds phosphate groups (PO4-) to specific proteins
known as synapins in the membrane of the synaptic vesicle.
- This permits the vesicle to undergo exocytosis and release its neurotransmitter molecules into the synapse.
- Ca+2 is then removed by absorption into mitochondria or transported to the ECF by an active calcium membrane
pump.
3. NT's bind with the protein receptor sites on the postsynaptic membrane, which has an effect on the membrane
potential of the postsynaptic neuron: hyperpolarize (inhibitory) or depolarize (excitatory).
- This alters their 3-D shape which leads to an ion channel opening, and the resulting current flows cause local
changes in the membrane potential.
4. The changes prompted by the NT-receptor binding are extremely brief because the NT is quickly removed from the
postsynaptic membrane by enzymatic degradation (destroyed) and then recycled by the presynaptic axon.
- e.g., acetylcholine (ACh) is decomposed by acetylcholinesterase (AChE), which prevents continual stimulation.
5. For each nerve impulse reaching the presynaptic terminal, many vesicles (perhaps 300) are emptied into the synaptic
cleft. The higher the frequency of impulses reaching the terminals (that is the more intense the stimulus), the greater
the total number of synaptic vesicles that fuse and spill their contents, and the greater the effect on the postsynaptic
cell—the more likely the graded potentials induce an AP at the axon hillock.
Synaptic Delay
1. Although some neurons can transmit impulses at rates that approach 300mi/hr, neural transmission across a
chemical synapse is comparatively slow and reflects the time required for 1) NR release, 2) diffusion across the
synapse, & 3) binding to receptors.
2. Typically, the synaptic delay in transmission lasts 0.3-0.5msec, and it is the rate-limiting step of neural transmission.
- Synaptic delay helps to explain why transmission along short neural pathways involving only 2 or 3 neurons
occurs rapidly, while that typical of higher mental functioning involving many neurons & synapses occurs much
more slowly. (However, in practical terms these differences are not noticeable.)
Postsynaptic Potentials & Synaptic Integration
1. There are 2 kinds of chemical synapses: excitatory & inhibitory.
- They are distinguished by how they affect the postsynaptic neuron. In both types, binding of NT's results in local
graded changes in the postsynaptic membrane potential.
2. At excitatory synapses, NT binding causes depolarization of the postsynaptic membrane.
- They aren't called action potentials, but instead are called excitatory postsynaptic potentials or EPSP's.
- Each EPSP lasts only a few ms and the membrane returns to its resting potential.
- It accomplishes this by opening a single type of protein channel that allows both Na + & K+ into the cell. Na+'s
gradient is greater than K+'s, so have greater influx of Na+ & depolarization occurs.
- Can depolarize above -55mV; however, postsynaptic membranes do not generate or transmit AP's, only axons
have this capability.
- If the currents reaching the axon hillock are strong enough to depolarize the axon to threshold, an action potential
will be generated.
- So, their primary function is to help trigger an AP distally at the axon hillock of the postsynaptic neuron.
3. At inhibitory synapses, NT binding causes hyperpolarization of the postsynaptic membrane.
- Fxns by making the membrane more permeable to K+, Cl-, or both. Na+ ion permeability is not affected.
- As K+ and/or Cl- move into the cell, the inside of the membrane is driven further away from the RMP and becomes
more negative (i.e., less likely to depolarize).
- potential drops from -70mV to -90mV, so a larger depolarizing current is required to induce an AP.
- These changes are called inhibitory postsynaptic potentials or IPSP's.
Physiology Bio2424
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Integration and Modification of Synaptic Events
1. The activity of a single excitatory axon terminal cannot induce an action potential in the postsynaptic neuron.
- But if 1000's of excitatory axon terminals are firing to the same postsynaptic membrane, or if a smaller number of
terminals are delivering impulses very rapidly, the probability of reaching threshold depolarization increases
greatly.
2. Thus EPSP's add together, or summate, to collectively influence the activity of a postsynaptic neuron. In fact, nerve
impulses would never be initiated if this were not so.
Two Types of Summation: applies to both EPSP's & IPSP's. Here we will use EPSP's as an example.
1. Temporal summation occurs when one or more presynaptic neurons transmit impulses in rapid-fire order and waves
of NT release occur in quick succession. The first impulse produces a slight EPSP, and before it dissipates,
successive impulses trigger more EPSP's. These summate, producing a greater depolarization of the postsynaptic
membrane than would result from a single EPSP.
2. Spatial summation occurs when the postsynaptic neuron is being stimulated by a large number of terminals from the
same or (more commonly) different neurons at the same time. As a result, huge numbers of its receptors bind
neurotransmitters and simultaneously initiate EPSP's, which sum up & dramatically increase the probability of the
axon hillock crossing, depolarizing to create an AP.
3. How is all the information sorted? It appears that each neuron's axon hillock keeps a "running account" of all the
signals it receives, so EPSP's & IPSP's summate separately and together. If the stimulatory effects of EPSP's
dominate the membrane potential enough to reach threshold, the neuron will fire. If, on the other hand, the summing
process yields only subthreshold depolarization or hyperpolarization, the neuron will fail to generate an AP.
Convergence & Divergence
1. Neurons are linked to each other through convergence & divergence to form complex nerve pathways.
2. Any given neuron may have many other neurons synapsing on it: convergence.
- Through this converging input, a single cell may be influenced by thousands of others.
- This single cell, in turn, influences the level of activity in many other cells by divergence of output.
3. Divergence refers to the branching of axon terminals, so that a single cell synapses with many other cells.
- Note that a particular neuron is postsynaptic to the neuron converging on it, but is presynaptic to the other cells on
which it terminates. Thus, the terms presynaptic & postsynaptic refer only to a single synapse.
- Most neurons are presynaptic to one group of neurons (the guys in front of them) and postsynaptic to another
group (the guys behind them).
4. There are an estimated 100 billion neurons in the brain alone each converging and diverging on many other
neurons—a very complex wiring system.
For the parasympathetic nervous system, describe the series of events of nerve transmission from the axon
hillock of the presynaptic neuron & ending at the axon hillock of the postsynaptic neuron:
AXON FUNCTION:  Very important…..that is why it is summarized….AGAIN!!!!
Functionally axons are impulse generators and conductors that transmit nerve impulses away from the neuron cell body to
effectors (other neurons, muscles, glands, organs).
1. Nerve impulses are called action potentials which is an electrical message used to transmit information from neuron
to neuron. A reverse of polarity of ions on either side of the cell membrane is the basis for the impulse.
2. The action potential is usually generated at the axon hillock and conducted along the axon to the axon terminals in a
one way direction.
3. There, it causes the release of chemicals called neurotransmitters into the synapse (synaptic cleft).
4. The neurotransmitters excite or inhibit the neurons (or effectors) with which the axon is in close contact. Since each
neuron both receives signals from and sends signals to scores of other neurons, it carries on “conversations” with
many different neurons at the same time.