Resting Membrane Potential Review
• Recall there is an uneven distribution of charged substances
(mainly ions) across the cell membrane of every cell in the
body which creates an electrical potential between the ICF
and ECF
• The ICF is negatively charged compared to the ECF
whereby a typical resting membrane potential (RMP) of –70
mV is established
Basis of the Resting Membrane Potential
• In all cells, Na+ and K+ are constantly pumped across the
cell membrane by the Na+,K+-ATPase maintaining:
– a high Na+ concentration in the ECF and a low Na+
concentration in the ICF
– a high K+ concentration in the ICF and a low K+
concentration in the ECF
• There is a constant diffusion of Na+ into the cell by:
• Na+ channels that are always open (leaky)
• There is a constant diffusion of K+ out of the cell by:
• open K+ channels that are always open (leaky)
• When a cell is at rest, the pumping of the Na+,K+-ATPase,
exactly equals the diffusion of Na+ and K+
– results in a steady state condition
Changes in the Resting Membrane Potential
• Many cells of the body use the electric potential across the
cell membrane to function
– the membrane potential changes from its resting value
due to a change in the environment of the cell
• the change in the membrane potential causes the cell
to “respond” to the change in its environment
• Changes in the membrane potential from resting values are
due to the function of gated ion channels
– these channels remain closed (while a cell is at rest) until
a change in the environment of the cell (STIMULUS)
causes them to open
Types of Gated Ion Channels
• Gated ion channels only allow the diffusion of 1
(sometimes 2) type of ion across the cell membrane
– Ligand-gated channels
• open when a specific chemical binds to the
extracellular portion of the channel
– Stretch-gated channels
• open when the plasma membrane is stretched
– Voltage-gated channels
• open when the membrane potential deviates from
resting and reaches a specific voltage
Gated Channels
• Channel types include some of the following examples
– Voltage-gated Ca2+ channels
– Stretch-gated Cl- channels
– Voltage-gated K+ channels
– Ligand-gated Na+ channels
• The diffusion of any additional ions across the plasma
membrane occurs at a much faster rate than the rate of
pumping of the Na+,K+-ATPase
– this causes the cell membrane potential to deviate from
the resting value
Operation of a Ligand-Gated Channel
Example: ligand-gated Na+ channel
• Closed when a chemical is NOT bound to the extracellular
portion of the channel
– Na+ cannot enter the cell
• Opens when a specific chemical attaches to the extracellular
portion of the channel
– Na+ diffuses into the cell
Operation of a Ligand-Gated Na+ channel
Deviations in the Resting Membrane Potential
• The opening of a gated ion channel will allow a specific ion
to diffuse down its respective gradient across the cell
membrane
• The membrane potential will deviate from the resting value
(-70mV) based on 2 criteria:
– the charge of the diffusing ion
• either positive (cation) or negative (anion)
– the direction of the diffusion
• either into or out of the cell
Deviations in the Resting Membrane Potential
• The ICF becomes less negative when:
– a cation diffuses into the cell
– an anion diffuses out of the cell
• depolarization
– reduces the polarity of the membrane as the
membrane potential moves toward 0mV
• The ICF becomes more negative when:
– a cation diffuses out of the cell
– an anion diffuses into the cell
• hyperpolarization
– increases the polarity of the membrane as the
membrane potential moves further away from 0mV
Deviations in the Resting Membrane Potential
• When the gated ion channels close, the cell membrane
potential returns to its resting value
Gated Channels and the Membrane Potential
• When gated channels open:
– ions move across the cell membrane down its
concentration gradient (HIGH → low)
– the number of ions that move across the membrane is
relatively small and thus DOES NOT CHANGE the
concentration gradient of the ion
• The membrane potential deviates because each ion has a
large charge associated with it
– the movement of only a “few” ions creates a large
change in the distribution of electric charge across the
cell membrane
• After the gated channels have closed, the “few” ions that
diffused are quickly moved up the gradient to return the
membrane potential to resting
Responses to Stimuli
• Stimulation of various cells (receptors/sensors) in the body
causes the opening of gated channels which changes in the
resting membrane potential initiating an electrical impulse
– ligand-gated channels are opened in taste buds by the
food that is ingested
– stretch-gated channels are opened in free nerve endings
in the dermis of the skin when bitten by a mosquito
– voltage-gated receptors are opened when your lab partner
uses an electrical stimulating electrode on your arm
Responses to Stimuli
• The electrical impulse travels from the stimulated receptor
cell to an effector cell (muscle and/or gland)
• A change in the membrane potential of the effector cell
causes a functional change in the cell allowing for an
appropriate response
– the salivary glands will secrete saliva into the mouth
while the tongue and muscles controlling the jaw will
contract, allowing you to chew and swallow or spit out
the ingested food
– the muscles controlling the arm and hand will contract,
allow you swat the mosquito
– the muscles of the hand will contract, causing the fingers
and wrist to flex
Neurons (Nerve Cells)
• The transfer of these electrical impulses over large distances
is accomplished by the cells of the nervous system called
neurons
– capable of:
• generating/initiating an electrical impulse
• sending electrical impulses very rapidly from one
location in the body to another
• changing the resting membrane potential of other cells
within the body including:
– other neurons
– effector cells of the body
• The nervous system is made up of millions of neurons that
connect all parts of the body to one another
The Nervous System
Neuron Anatomy
• Dendrites
– branched appendages that receive stimuli
– respond to a stimuli by opening gated channels
• location of stretch or ligand-gated channels
• change in the membrane potential of the neuron at the
precise location of the stimulus on the cell
• Body (soma)
– location of organelles, but can also receive stimuli
– respond to a stimuli by opening gated channels
• location of stretch or ligand-gated channels
• change in the membrane potential of the neuron at the
precise location of the stimulus on the cell
• Axon
– long extension of the cell body, that can branch many
times which sends the electrical impulse to other cells in
the body
• location of voltage-gated channels
Neuron
Initiation of an electrical impulse
• The initiation of an electrical impulse occurs at either the
dendrites or the body of a neuron
– the opening of stretch or ligand-gated channels causes
EITHER a depolarization or a hyperpolarization,
depending on the charge and the direction of movement
of the ion at the location of the opened gated channels
• this type of membrane potential change is called a
graded (local) potential
– a brief, localized change in the membrane potential
Graded Potentials
• The grade or magnitude of depolarization or
hyperpolarization is directly related to the size of the
stimulus
– determines the number of gated channels that is opened
• determines the number of ions that cross the plasma
membrane
Graded Potentials of Stretch-gated Channels
• A small pressure applied to the skin:
– causes a small amount of stretch of the cell membrane of
the pressure sensing cells of the skin
• causes few stretch-gated channels to open
– allows few ions to cross the cell membrane
• causes a small change of the membrane
potential from the resting value
• A large pressure applied to the skin:
– causes a large amount of stretch of the cell membrane of
the pressure sensing cells of the skin
– causes more stretch-gated channels to open
– allows more ions to cross the cell membrane
• causes a larger change of the membrane
potential from the resting value
Graded Potentials
• Decrease in magnitude with distance from the site of
stimulation
– as ions move into/out of the cell through opened gated
channels, they diffuse away from the opened gated
channel
• as the ions diffuse away from the opened gated
channel the concentration of the ion decreases
– as the ion concentration decreases, so does it’s
influence on the membrane potential
• the further away from the stimulus, the closer
the membrane potential is to the resting value
Function of Graded Potentials
• The purpose of graded potentials in the dendrites or soma is
to cause (or prevent) the opening of voltage-gated ion
channels in the axon of the neuron
– open when the membrane potential in the axon has been
depolarized to a minimum value
– the opening of voltage-gated channels in the axon will
create a membrane potential change in the axon called an
action potential
• the action potential will “travel” down the length of
the axon and all of its branches to the axon terminus
Action Potentials (APs)
• A very rapid sequence of membrane potential changes due
to the opening and closing of voltage-gated Na+ and
voltage-gated K+ channels
• There are 3 sequential phases to an AP in a neuron:
– Depolarization
• a reduction in the polarity of the membrane potential
– Repolarization
• a return of the membrane potential towards the resting
value
– Hyperpolarization
• the membrane potential reaches values more negative
than the resting value
• All APs in a neuron have the same magnitude regardless of
the size of the stimulus (not graded)
Action
potential
Threshold and Action Potentials
• The initiation of an AP occurs at the beginning of the axon
called the initial segment and requires that the membrane
potential at the axon be depolarized to threshold
– the minimum amount of depolarization required to
initiate an action potential
• typically -55mV
• causes the opening of voltage-gated Na+ channels
Threshold and Action Potentials
• Threshold can be reached by a depolarizing graded potential
in the dendrites or soma of a neuron
– small (weak) stimuli DO NOT initiate an AP because the
magnitude of the graded potential at the axon is TOO
SMALL to depolarize the membrane at the axon to
threshold
• subthreshold stimuli
– large (strong) stimuli DO initiate an AP
• threshold stimuli
• All-or-none phenomenon
– action potentials either completely, or not at all
Ionic Basis of Action Potential (Resting State)
• Na+ and K+ channels are closed
Ionic Basis of Action Potential (Depolarization)
If a strong enough stimulus is presented to the cell, the
membrane potential depolarizes to threshold
(-55mV) causing:
– Na+ channels to open
• Na+ enters the cell (diffusion)
– membrane potential continues to depolarize to
+30mV
• K+ channels slowly
begin to open
Ionic Basis of Action Potential (Repolarization)
Membrane potential reaches peak depolarization of +30mV
causing:
• Na+ channels to close
• K+ channels to open
– K+ exits the cell (diffusion)
• the membrane potential
returns toward resting
values (repolarization)
Ionic Basis of Action Potential
(Hyperpolarization and Return to Resting)
• K+ channels remain open
• This causes more than enough K+ to leave the cell resulting
in hyperpolarization of the membrane potential
• Eventually, the K+
channels
close, allowing the
membrane potential to
return to resting
Refractory Periods
Absolute Refractory Period
• The absolute refractory period:
– is the time during an action potential that another action
potential CANNOT be initiated
• no matter how strongly the dendrites/soma are
stimulated
– ensures that each action potential created is separated
from one another so that the body can interpret stimuli
accurately
– is time required for the voltage-gated Na+ channels to be
“reset”
• required for the channels to open again
Relative Refractory Period
• The relative refractory period:
– is the time after the absolute refractory period until the
membrane potential returns to the resting value
• During this time another action potential CAN be initiated
– requires a stronger than normal stimulus at the dendrites
• during this time some of the voltage-gated Na+
channels have been “reset” while others have not
Propagation of an Action Potential
• Once an action potential has been initiated at the beginning
of the axon, it must “travel” (propagate) along the length of
the axon to the axon terminus
• The influx of Na+ into the cell during depolarization causes
the membrane potential in “front” of the opened Na+
channels to depolarize to threshold
• Reaching threshold opens up the Na+ channels in “front” of
the site of the action potential causing an action potential to
be created in this new location
• As the next group of Na+ channels begins to open, the ones
“behind” them are closing
• The impulse continues to propagate away from its point of
origin to the axon terminus
• “the domino effect”
Propagation of an
Action Potential
Propagation Velocity of an Action Potential
• The propagation velocity is the speed at which the action
potential propagates along the length of the axon
• Conduction velocity depends on:
– axon diameter (thickness)
• the larger the diameter, the greater the conduction
velocity
– presence of a myelin sheath
• dramatically increases impulse speed
– to speeds up to 300 mph
• more effective than increasing axon diameter
• The human body uses both methods to maximize
propagation velocity
Myelin Sheath
• White, fatty (lipid), segmented covering around most long
axons
• Increases propagation velocity of APs by electrically
insulating the axon
• Formed by Schwann cells
– wraps around the axon many times with its plasma
membrane
– encloses the axon with many concentric layers of lipid
bilayers
Myelin Sheath
Myelin Sheath Formation
Nodes of Ranvier
• The nodes of Ranvier are:
– gaps between the Schwann cells
• naked axon segments
– the ONLY locations of voltage-gated Na+ and K+
channels
• in large densities
• ONLY locations where an AP can be generated along
the length of the axon
Saltatory Conduction
• Ions pass through a myelinated axon only at the nodes of
Ranvier creating an action potential
– due to the large density of voltage-gated Na+ channels
creates a large electrical field surrounding the node
• causes the cell membrane to reach to threshold at a
large distance away (the next node)
– creates and AP at the next node
• The action potential jumps from node to node
– much faster conduction rate compared to unmyelinated
axons (of the same diameter)
Nodes of Ranvier and Saltatory Conduction
Saltatory Conduction
Axon Termini and Synapses
• When the AP reaches the axon termini the impulse must be
transmitted to the next cell in the path to the effector
• A synapse is the junction between 2 cells where the impulse
is transmitted from one cell to another :
– Presynaptic cell (before synapse)
– Postsynaptic cell (after synapse)
– found between:
• 2 neurons
• a neuron and an effector cell (muscle or gland)
– 2 general types include:
– chemical
– electrical
Axon Termini and Synapses
Chemical Synapses
• Composed of 3 parts:
– axonal terminal of the presynaptic neuron
• contains synaptic vesicles
– filled with a neurotransmitter (chemical/ligand)
– receptor region on the postsynaptic cell which contains
ligand-gated channels
– fluid-filled space between the cells (synaptic cleft)
• separates the presynaptic and postsynaptic cells
Chemical Synapse
Synaptic Cleft: Information Transfer
• An action potential that arrives at the axon terminus of the
presynaptic cell causes the opening of voltage-gated Ca2+
channels
– causes Ca2+ to diffuse into the cytoplasm of the
presynaptic cell
• triggers the exocytosis of neurotransmitters into the
synaptic cleft
• The neurotransmitters diffuse across the cleft and open the
ligand-gated channels on the postsynaptic cell
– causes ions to cross the cell membrane and result in a
graded potential
• postsynaptic potential
– depolarization or hyperpolarization
Synaptic Cleft: Information Transfer
Postsynaptic Potentials
The 2 types of postsynaptic potentials are:
• EPSP (excitatory postsynaptic potentials)
– depolarizing graded potentials
– causes the membrane potential move towards threshold
which increases the chances that an AP will be initiated
in an axon
• IPSP (inhibitory postsynaptic potentials)
– hyperpolarizing graded potentials
• causes the membrane potential move away from
threshold which reduces the chances that an AP will
be initiated in an axon
Excitatory and Inhibitory Postsynaptic Potentials
EPSPs and IPSPs Summate
• A single EPSP CANNOT initiate an action potential
– EPSPs must summate (add) to bring the membrane
potential to threshold at the axon
• Temporal summation
– postsynaptic potentials are generated at a single location
at a high frequency
• Spatial summation
– postsynaptic potentials are generated at different
locations at the same time
• IPSPs can also summate with EPSPs
– cancel each other out
Temporal Summation
Temporal
Summation
Spatial Summation