MEMBRANE POTENTIALS

Topic Content Table

MEMBRANE POTENTIAL

1. RESTING MEMBRANE POTENTIAL:

1.1. Equilibrium Potentials, the Na+/K+ pump and the RMP

1.2. Approximation of RMP by Nernst Equation:

1.3. Different Cells have Different RMP’s Values:

2. GRADED POTENTIAL AND ACTIONS POTENTIALS

2.1 GRADED POTENTIAL

2.1.1. Excitatory Postsynaptic Potentials (EPSPs)

2.1.2. Inhibitory Post Synaptic Potentials (IPSPs)

2.1.3. The Integration of Postsynaptic Potentials and the Generation of

Action Potentials

2.2. ACTION POTENTIAL

2.2.1. Voltage-Gated Sodium and Potassium Channels

2.2.2. Voltage-Gated Potassium Channel and Its Activation

2.2.3. Roles of Other Ions during the Action Potential

2.2.4. The General Sequence Events of an Action Potential

2.2.5. Initiation of Action Potentials

2.2.6. Summation

3. COMPARISON OF GRADED AND ACTION POTENTIALS

REFERENCES

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MEMBRANE POTENTIALS

MEMBRANE POTENTIAL

The Membrane Potential of a cell describes the separation of

opposite charges across the plasma membrane. The sketch below

shows the relative difference chemically and electrically

between the inside and outside of any living cell. As we know

Potential Energy (stored energy) is the capacity to do work, the

capacity for energy exchange. The amazing thing about living

cells is that they have potential energy set up across their plasma

membranes, which allows cells to do work. The membrane

potential of a cell has a slight imbalance in electrical charge

across the plasma membrane, that is, the cell is slightly

negative on the inside and slightly positive on the outside (Fig.1)

1.RESTING MEMBRANE POTENTIAL:

Resting membrane potential can be defined as a relatively stable, ground value of trans-

membrane voltage in animal and plant cells. At 'rest' the cell maintains an electrical and

chemical disequilibrium. For Neurons, the RMP = -70 m V. This is a relative measure of

the voltage inside of the cell; the negative value indicates that the inside is negative relative

to the outside. (Fig. 2)

Following are the two Ionic Basis of the

Resting Membrane Potential

1. Ions (Na+, K+ , Cl-, A--)The membrane potential results

from the distribution of positively

and negatively charged particles

called ions. There are 4 kinds of

ions that contribute to the resting

membrane potential: Sodium

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Figure 1: Membrane Potential

Figure 2: Resting Membrane Potential

MEMBRANE POTENTIALS

(Na+), potassium (K+), chloride (Cl-), and negatively charged protein ions

sometimes called Anions (A--).

The concentration of Na+ and Cl- ions are greatest outside of the resting cell,

whereas the concentrations of K+ is greatest inside the cell and negatively charged

protein ions which are synthesized inside the neuron are trapped there. These ions

concentrations from one side of the cell membrane to the other are different and

cause chemical gradient or disequilibrium.

2. Differential permeabilityThe neuronal membrane is porous (i.e., contains ion channels) and allows certain

ions to pass in and out of the cell more readily than others. This passive property of

the cell membrane is called differential permeability and contributes to the

polarized resting potential. For example, both K+ and Cl- ions readily diffuse

through the neural membrane; Na+ ions diffuse with more difficulty and anions

cannot diffuse at all. The electrical charge they contribute from one side of the cell

membrane to the other also differs. This is referred as electrical gradient or

disequilibrium.

Table. 1: A comparison of the permeabilities of ions responsible for creating the

membrane potential.

Ion ECF Concentration (mM)

ICF Concentration (mM)

Permeability

Na+ 150 15 1

K+ 5 150 50-75

Pro- 0 65 0

As Table 1 above shows, K+ is the most permeable of the ions. In this way, K+ is the most

influential ion in establishing the RMP.

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MEMBRANE POTENTIALS

1.1. Equilibrium Potentials, the Na+/K+ pump and the RMP If we examine the equilibrium potential of the important ions

Na+ and K+ it nicely illustrates how the differences in permeabilities of these

ions contribute to the value of the RMP. To understand the equilibrium

potentials for Na+ and K+ ions, we must examine a hypothetical cell and assume

in each case (separately) that the Na+ and K+ ions are freely permeable, thus can

cross the cell membrane freely.(Fig. 3)

1.1.1. The Movement of Na+ ions

alone: If it is assumed that Na+ ions

are freely permeable, with no

restrictions to its movement, then Na+

ions will move back and forth across

the membrane until the Electrochemical

Gradient has Equilibrated. The value

of the voltage across the membrane for

the Equilibrium Potential of Na+ = +60 mV (ENa+ = +60mV)

1.1.2. The movement of K+ ions alone: If it is assumed that K+ ions are freely

permeable, with no restrictions to its movement, then K+ ions will move back

and forth across the membrane until the Electrochemical Gradient has

Equilibrated. The value of the voltage across the membrane for the Equilibrium

Potential of K+ = -90 mV (EK+ = -90m V) If these ions were both equally

permeable, then the RMP would be somewhere in between these two values (in

between -90 and +60 mV). However, K+ ions are 50 to 75 times more

permeable than Na+ and therefore the RMP is much closer to the EK+ than the

ENa+. The value of -70 mV is much closer to -90mV than to +60 mV.

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Figure 3: Different Ions Contribution in RMP)

MEMBRANE POTENTIALS

1.1.3. The Na+/ K+ Pump (also called the Na+/K+ ATPase): A transport

membrane spanning protein embedded in the plasma membrane that 'pumps'

Na+ and K+ ions across the

membrane against their

concentration gradients. To do

this, it requires ATP directly,

and so it is a primary active

transport mechanism. It pumps

out or ejects 3 Na+ ions from the

inside of the cell and pumps in

or imports 2K+ into the cell from

the outside at the cost of 1 ATP for one cycle of the Na+/K+ pumps. The pump is

a protein that has catalytic ability (is an enzyme as well) and hydrolyzes ATP to

ADP + Pi and heat. (Fig. 4)

Both Na+ and K+ ions continuously "leak" across the cell membrane down their

concentration gradients (through open protein channels or ‘pores’ in the

membrane). Because of this, the Na+/ K+ pump must be active all the time in

order to constantly bailout the leaky ship and maintain the RMP. In summary, it

is these three issues that contribute to the maintenance of the RMP.

1.2. Approximation of RMP by Nernst Equation:

RMP Approximation for the equilibrium potential of a given ion only needs the

concentrations on either side of the membrane and the temperature. It can be calculated

using the Nernst equation:

Where

Eeq,K+ is the equilibrium potential for potassium, measured in volts

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Figure 4

MEMBRANE POTENTIALS

R is the universal gas constant, equal to 8.314 joules·K−1·mol−1

T is the absolute temperature, measured in kelvins (= K = degrees Celsius + 273.15)

z is the number of elementary charges of the ion in question involved in the reaction

F is the Faraday constant, equal to 96,485 coulombs·mol−1 or J·V−1·mol−1

[K+]o is the extracellular concentration of potassium, measured in mol·m−3 or

mmol·l−1

[K+]i is likewise the intracellular concentration of potassium

Potassium equilibrium potentials of around −80 millivolts (inside negative) are common.

Differences are observed in different species, different tissues within the same animal, and

the same tissues under different environmental conditions. Applying the Nernst Equation

above, one may account for these differences by changes in relative K+ concentration or

differences in temperature.

Common usage of the Nernst equation is often given in a simplified form by assuming

typical human body temperature (37 °C), reducing the constants and switching to Log base

10. (The units used for concentration are unimportant as they will cancel out into a ratio).

For Potassium at normal body temperature one may calculate the equilibrium potential in

millivolts as:

Likewise the equilibrium potential for sodium (Na+) at normal human body temperature is

calculated using the same simplified constant. You can calculate E assuming an outside

concentration, [K+]o, of 10mM and an inside concentration, [K+]i, of 100mM. For chloride

ions (Cl−) the sign of the constant must be reversed (−61.54 mV). If calculating the

equilibrium potential for calcium (Ca2+) the 2+ charge halves the simplified constant to

30.77 mV. If working at room temperature, about 21 °C, the calculated constants are

approximately 58 mV for K+ and Na+, −58 mV for Cl− and 29 mV for Ca2+. At

physiological temperature, about 29.5 °C, and physiological concentrations (which vary for

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MEMBRANE POTENTIALS

each ion), the calculated potentials are approximately 67 mV for Na+, −90 mV for K+,

−86 mV for Cl− and 123 mV for Ca2+.

1.3. Different Cells have Different RMP’s Values:Mainly 4 types of primary tissues are found in the human body that mainly contributes

toward the overall functionality of the body:

1. Epithelium Tissue

2. Connective Tissue

3. Muscle Tissue*

4. Nervous Tissue*

*indicating tissue excitable tissue which respond to the excitement.

The excitable tissues have various RMP's, for example; neurons have a RMP of -70mV

whereas most cardiac muscle cells have a RMP of -90mV. Excitable means that they are

capable of producing electrical signals when excited. As we know the flow of charged

particles is an electrical current, and these currents are used to send signals or do work.

Table.2: Resting potential values in different types of cells

Cell types Resting potential

Skeletal muscle cells −95 mV

Smooth muscle cells –60 mV

Astroglia –80 to –90 mV

Neurons –60 to –70 mV

Erythrocytes –9 mV

Photoreceptor cells –40 mV

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MEMBRANE POTENTIALS

2. GRADED POTENTIAL AND ACTIONS POTENTIALS

Neurons are the basic cell of communication in the Nervous System, There are two ways

that a neuron can undergo rapid changes in RMP and this really means that there are two

ways that neurons can be electrically communicated. These ways include following main

types of membrane potentials:

1. Graded Potentials

2. Action Potentials.

2.1. GRADED POTENTIAL Graded potentials are Local change in membrane potential with variable

degrees of magnitude and die out within 1 to 2 mm of their site of origin. They are

usually produced by some specific change in the cell’s environment acting on a

specialized region of the membrane, and they are called “graded potentials” simply

because the magnitude of the potential change can vary (is graded). These are means for

short distance communication. We encounter a number of graded potentials, which are

given various names related to the location of the potential or to the function it performs:

receptor potential, synaptic potential, and pacemaker potential. (Fig. 5)

Let us have brief Introduction of each type of these potentials.

1. Synaptic potential: A graded potential change produced in the

postsynaptic neuron in response to release of a neurotransmitter by a

presynaptic terminal; it may be depolarizing (an excitatory postsynaptic

potential or EPSP) or hyperpolarizing (an inhibitory postsynaptic potential or

IPSP).

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MEMBRANE POTENTIALS

2. Receptor potential: A graded potential produced at the peripheral endings

of afferent neurons (or in separate receptor cells) in response to a stimulus.

3. Pacemaker potential: A spontaneously occurring graded potential change

that occurs in certain specialized cells.

These potentials arise from the summation of the individual actions of ligand-gated ion

channel proteins, and decrease over time and space. They do not typically involve voltage-

gated sodium and potassium channels. These impulses are incremental and may be

excitatory or inhibitory.

Figure 5: Graded Potential

They particularly occur at the postsynaptic dendrite as a result of presynaptic neuron firing

and release of neurotransmitter, or may occur in skeletal, smooth, or cardiac muscle in

response to nerve input. The magnitude of a graded potential is determined by the strength

of the stimulus.When neurotransmitter molecules bind to postsynaptic receptors, they

have one of two effects: depolarization or hyperpolarization.

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MEMBRANE POTENTIALS

1.Depolarizations are called Excitatory postsynaptic potentials (or EPSPs) because

they increase the likelihood that the neuron will fire;

2.Hyperpolarizations are called Inhibitory postsynaptic potentials (IPSPs) and

decrease the likelihood that the neuron will fire.

Both events are graded potentials because the strength of their effects are proportional to

the intensity of the signal.EPSPs and IPSPs travel passively through the neuron like an

electrical signal travels through a cable. This result in rapid transmission that is

decremental i.e., the signal gets weaker (decreases in amplitude) the farther it travels. (Fig.

6a & 6b)

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MEMBRANE POTENTIALS

2.1.1. Excitatory Postsynaptic Potentials (EPSPs)

Graded potentials

that make the

membrane

potential less

negative or more

positive, thus

making the

postsynaptic cell

more likely to have an action potential, are called excitatory postsynaptic

potentials (EPSPs). Depolarizing local potentials sum together, and if the

voltage reaches the threshold potential, an action potential occurs in that cell.

EPSPs are caused by the influx of Na+ or Ca+2 from the extracellular space into

the neuron or muscle cell. When the presynaptic neuron has an action potential,

Ca+2 enters the axon terminal via voltage-dependent calcium channels and

causes exocytosis of synaptic vesicles, causing neurotransmitter to be released.

The transmitter diffuses across the synaptic cleft and activates ligand-gated ion

channels that mediate the EPSP. The amplitude of the EPSP is directly

proportional to the number of synaptic vesicles that were released.

If the EPSP is not large enough to trigger an action potential, the membrane

subsequently repolarizes to its resting membrane potential. This shows the

temporary and reversible nature of graded potentials.

2.1.2. Inhibitory Post Synaptic Potentials (IPSPs) Graded potentials that make the membrane potential more negative,

and make the postsynaptic cell less likely to have an action potential, are called

inhibitory post synaptic potentials (IPSPs). Hyperpolarization of membranes is

caused by influx of Cl− or efflux of K+. As with EPSPs, the amplitude of the

IPSP is directly proportional to the number of synaptic vesicles that were

released.

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Figure 6a Figure 6b

MEMBRANE POTENTIALS

2.1.3. The Integration of Postsynaptic Potentials and the Generation of

Action Potentials Each neuron receives thousands of synaptic contacts which produce

graded potentials. Whether or not a neuron fires depends on the summation of

the signals that reach the axon hillock. The integration of graded potentials

summates in two ways: temporally and spatially (Fig. 7).

1. Temporal summation refers to the combining of signals from a single

synapse across time. The potentials summate because there is a greater

number of open ions channels and, therefore a greater flow of positive

ions into the cell.

2. Spatial summation refers to the combination of signals from different

synapses that are located in close proximity to each other.

3. If the combined stimulation results in a sufficient depolarization at the

hillock then the neuron will generate an action potential; the threshold

of excitation is about -65mV for many neurons.

In graded potentials because the electric signal decreases with distance, they

can function as signals only over very short distances (a few millimeters).

Nevertheless, graded potentials are the only means of communication used by

some neurons and, as we shall see, play very important roles in the initiation

and integration of the long-distance signals by neurons and some other cells.

Stronger the triggering event, the stronger the graded potential.

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Figure 7

MEMBRANE POTENTIALS

What is a trigger? Here are some examples of what can trigger a graded

potential:

1. A Specific Stimulus - a change in temperature, pH, light intensity, etc.

2. A Surface Receptor on plasma membrane - binding of the receptor by a

ligand.

3. Spontaneous change in membrane potential - may be caused by 'leaky'

channels, etc.

2.2. ACTION POTENTIAL

Action Potential = a brief reversal of resting membrane potential

by a rapid change in plasma membrane permeability. 'Reversal' => from -70mV to +30mV

back to -90mV. Nerve and muscle cells as well as some endocrine, immune, and

reproductive cells have plasma membranes capable of producing action potentials. These

membranes are called excitable membranes, and their ability to generate action potentials is

known as excitability. Whereas all cells are capable of conducting graded potentials, only

excitable membranes can conduct action potentials. The propagation of action potentials is

the mechanism used by the nervous system to communicate over long distances.

The spread of an action potential is non-decremental, that is, the strength of the signal does

not diminish over distance, and it is maintained from the site of origin to destination. An

action potential can be described as an All or None event. During an action potential,

significant changes occur in membrane permeability for Na+ and K+. This causes rapid

fluxes of theses ions down their electrochemical gradients.

There are 4 main phases of an action potential:

1. Threshold

2. Depolarization phase

3. Repolarization phase

4. Hyperpolarization phase

For an action potential to occur, threshold must be reached. The threshold value in neurons

is -55 mV. When the RMP is altered and it reaches threshold, this change in the voltage of

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MEMBRANE POTENTIALS

the membrane causes voltage gated Na+ channels to open, and this triggers the onset of an

action potential (Fig. 8)

Resting Stage. This is the resting membrane potential before the action potential begins.

The membrane is said to be “polarized” during this stage because of the –90 millivolts

negative membrane potential that is present.

Depolarization Phase. At this time, the

membrane suddenly becomes very permeable to

sodium ions, allowing tremendous numbers of

positively charged sodium ions to diffuse to the

interior of the axon. The normal “polarized”

state of –90 millivolts is immediately neutralized

by the inflowing positively charged sodium ions,

with the potential rising rapidly in the positive

direction. This is called depolarization. In large nerve fibers, the great excess of positive

sodium ions moving to the inside causes the membrane potential to actually “overshoot”

beyond the zero level and to become somewhat positive. In some smaller fibers, as well as

in many central nervous system neurons, the potential merely approaches the zero level and

does not overshoot to the positive state.

Repolarization Phase. 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 more than normal. Then, rapid diffusion of potassium ions to

the exterior re-establishes the normal negative resting membrane potential. This is called

repolarization of the membrane.

To explain more fully the factors that cause both depolarization and repolarization, we need

to describe the special characteristics of other types of transport channels through the nerve

membrane.

2.2.1. Voltage-Gated Sodium and Potassium Channels

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Figure 8: Different Stages of Action Potential

MEMBRANE POTENTIALS

The necessary in causing both depolarization and repolarization of the nerve

membrane during the action potential is the voltage-gated sodium channel. A voltage-

gated potassium channel also plays an impor- tant role in increasing the rapidity of

repolarization of the membrane. These two voltage-gated channels are in addition to the

Na-K pump and the K-Na leak channels (Fig. 9).

Voltage-Gated Sodium Channel—Activation and Inactivation of

the Channel This channel has two gates—one near the outside of the channel

called the activation gate, and another near the inside called the inactivation gate.

In the normal resting membrane when the membrane potential is –90 millivolts,

the activation gate is

closed, which prevents

any entry of sodium ions

to the interior of the fiber

through these sodium

channels.

Activation of the

Sodium Channel. When the membrane

potential becomes less

negative than during

the resting state, rising

from –90 millivolts

toward zero, it finally

reaches a voltage—

usually somewhere between –70 and –50 millivolts—that causes a sudden

conformational change in the activation gate, flipping it all the way to the open

position. This is called the activated state; during this state, sodium ions can pour

inward through the channel, increasing the sodium permeability of the membrane

as much as 500- to 5000-fold.

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Figure 9

MEMBRANE POTENTIALS

Inactivation of the Sodium Channel. The same increase in voltage that

opens the activation gate also closes the inactivation gate. The inactivation gate,

however, closes a few 10,000ths of a second after the activation gate opens. That

is, the conformational change that flips the inactivation gate to the closed state is a

slower process than the conformational change that opens the activation gate.

Therefore, after the sodium channel has remained open for a few 10,000ths of

a second, the inactivation gate closes, and sodium ions no longer can pour to the

inside of the membrane. At this point, the membrane potential begins to recover

back toward the resting membrane state, which is the repolarization process.

Another important characteristic of the sodium channel inactivation process is that

the inactivation gate will not reopen until the membrane potential returns to or

near the original resting membrane potential level. Therefore, it usually is not

possible for the sodium channels to open again without the nerve fibers first

repolarizing.

2.2.2. Voltage-Gated Potassium Channel and Its Activation

During the resting state, the gate of the potassium channel is closed, and potassium ions are

prevented from passing through this channel to the exterior. When the membrane potential

rises from –90 millivolts toward zero, this voltage change causes a conformational opening

of the gate and allows increased potassium diffusion outward through the channel.

However, because of the slight delay in opening of the potassium channels, for the most

part, they open just at the same time that the sodium channels are beginning to close

because of inactivation. Thus, the decrease in sodium entry to the cell and the simultaneous

increase in potassium exit from the cell combine to speed the repolarization process,

leading to full recovery of the resting membrane potential within another few 10,000ths of

a second.

2.2.3. Roles of Other Ions during the Action Potential

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MEMBRANE POTENTIALS

Two other types of ions must be considered: negative anions and calcium

ions for the action potentials of the membranes.

Negatively Charged Ions inside the Nerve Axon. Inside the axon there are many

negatively charged ions that cannot pass through the membrane channels. They include the

anions of protein molecules and of many organic phosphate compounds, sulfate

compounds, and so forth. Because these ions cannot leave the interior of the axon, any

deficit of positive ions inside the membrane leaves an excess of these impermeant negative

anions. Therefore, these impermeant negative ions are responsible for the negative charge

inside the fiber when there is a net deficit of positively charged potassium ions and other

positive ions.

Calcium Ions. The membranes of almost all cells of the body have a calcium pump

similar to the sodium pump, and calcium serves along with sodium in some cells to cause

most of the action potential. Like the sodium pump, the calcium pump pumps calcium ions

from the interior to the exterior of the cell membrane (or into the endoplasmic reticulum of

the cell), creating a calcium ion gradient of about 10,000-fold. This leaves an internal cell

concentration of calcium ions of about 10–7 molar, in contrast to an external concentration

of about 10–3 molar.

In addition, there are voltage-gated calcium channels. These channels are slightly

permeable to sodium ions as well as to calcium ions; when they open, both calcium and

sodium ions flow to the interior of the fiber. Therefore, these channels are also called

Ca-Na channels. The calcium channels are slow to become activated, requiring

10 to 20 times as long for activation as the sodium channels. Therefore, they are called

slow channels, in contrast to the sodium channels, which are called fast channels. Calcium

channels are numerous in both cardiac muscle and smooth muscle. In fact, in some types of

smooth muscle, the fast sodium channels are hardly present, so that the action potentials are

caused almost entirely by activation of slow calcium channels

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MEMBRANE POTENTIALS

2.2.4. The General Sequence Events of an Action Potential The result of the opening of voltage gated Na+ channels when

threshold is reached (and the positive feedback loop that ensues) is that Na+ floods into cell

and the inside of the cell becomes more positive very quickly, going from -55 mV (resting)

towards a positive value of +30 mV. Recall that the ENa+ = +60 mV, therefore the

membrane is getting closer to this value. At the 'Peak' of the action potential (+30mV), the

Na+ channels close (become deactivated) and remain closed and inactive until RMP is

restored.

All the while, the slow to open K+ channels continue to open and at the peak of the action

potential K+ rush out of the cell, down their concentration gradient. This outward

movement of K+ starts to restore membrane potential back toward RMP (the membrane

voltage is decreasing now but the potential is increasing). This is the repolarization phase;

the cell is becoming more negative inside as the positively charged K+ leaves the cell.

These K+ channels are also slow to close and continue to allow the positively charged K+ to

leave the cell. This leads to a more negatively charged cell inside and represents the

Hyperpolarization phase of the action potential. As the slow closing K+ finally close, the

resting permeability of the cell is restored, RMP is restored and the action potential is over.

An Action Potentials has 2 Refractory Periods

1. Absolute Refractory Period: During this period, the cell is unresponsive to any further

stimuli. No other action potential can be fired at this point, regardless of the strength of the

stimuli. The role of the Absolute refractory period is to ensure one-way propagation of

action potentials.

2. Relative Refractory Period: During this period, another action potential can be

produced but the strength of the stimuli must be greater than normal to trigger an action

potential. The role of the Relative refractory period: helps to limit the frequency of action

potentials.

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MEMBRANE POTENTIALS

2.2.5. Initiation of Action Potentials

Stimuli” is the initiators of action potentials. Various types of neurons generate action

potentials which can be summarized as fellow (Fig. 10)

In afferent neurons, the initial

depolarization to threshold is achieved

by a graded potential—here called a

receptor potential, which is generated

in the sensory receptors at the

peripheral ends of the neurons. These

are the ends farthest from the central

nervous system, and where the nervous

system functionally encounters the

outside world. In all other neurons, the

depolarization to threshold is due

either to a graded potential generated

by synaptic input to the neuron or to a

spontaneous change in the neuron’s

membrane potential, known as a

pacemaker potential. Spontaneous

generation of pacemaker potentials

occurs in the absence of any identifiable external stimulus and is an inherent property of

certain neurons (and other excitable cells, including certain smooth- muscle and cardiac-

muscle cells). In these cells, the activity of different types of ion channels in the plasma

membrane causes a graded depolarization of the membrane—the pacemaker potential. If

threshold is reached, an action potential occurs; the membrane then depolarizes and again

begins to depolarize. There is no stable, resting membrane potential in such cells because

of the continuous change in membrane permeability. The rate at which the membrane

depolarizes to threshold determines the action-potential frequency. Pacemaker potentials

are implicated in many rhythmical behaviors, such as breathing, the heartbeat, and

movements within the walls of the stomach and intestines.

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Figure 10

MEMBRANE POTENTIALS

2.2.6. Summation:

Summation is when the magnitude of graded potentials can be added together, to have a

combined effect on the postsynaptic membrane. Summation of graded potentials can occur

in two ways: Temporal Summation and Spatial Summation.

Temporal Summation occurs from the summation of graded potentials overlapping in

time. In other words (using the example in class), as the frequency of signals (action

potentials) from neuron A to another neuron, (neuron X) increases, the graded potentials

(from A) can summate.

Spatial Summation occurs from the summation of several graded potentials from several

converging neurons simultaneously. In other words (again using the example in class),

when several different neurons in space (e.g., A and B) send a signal simultaneously to

neuron X, these graded potentials that are sent at the same time are summated by neuron X.

Speed of the Conduction of the Signal

Although the magnitude of an action potential is always the same, the speed of the

propagation of an action potential down an axon can vary.

1. Diameter of Axon

Compare the cross sectional diameter of axons A and B.

Which of these axons will conduct a signal faster and why?

A B

The larger axon will conduct a signal faster than a smaller axon. This is because there is

less friction between the moving charged particles (Na+ and K+) and the sides of the axon in

the larger axon. Axons in the human body do vary in their diameter, but there is a limit to

how large the diameter of an axon can be within the confines of the entire human body.

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MEMBRANE POTENTIALS

2. Temperature

When the surrounding temperature increases, chemical reactions speed up. Thus, if axon

temperatures increase, the rate of conduction of the impulse down the axon will increase.

Conversely, if temperatures decrease, the rate of conduction of the impulse down the axon

will also decrease. Normally, body temperature remains very constant but can change

dramatically in some situations. Typically a dramatic drop in Tb will significantly slow

down neuronal transmission. For example, if a person falls into the very cold water of a

frozen over lake, all of their nervous responses will be significantly slowed.

3. Myelination of Axon

The myelin sheath that covers some axon is made from the cytoplasm of glial cells

(Schwann cells in the PNS and oligodendrocytes in the CNS). The myelin sheath is mostly

composed of lipids and therefore is a good insulator, which is the same as saying it is a

poor conductor of electrical charge. In this way, it reduces the electrical 'leakiness' along

the axon and helps to conduct the signal more quickly.

Little gaps in the myelin sheath, called 'Nodes of Ranvier', allow the action potential to

move faster along the axon. The electrical signal is said to jump from node to node, thus it

is called Saltatory Conduction. This is not what actually happens at the Nodes of Ranvier,

but at this stage it is convenient to think of the signal 'jumping' down the myelinated axon

significantly faster than a non-myelinated axon.

Of these three factors that can affect the speed of an action potential traveling down an

axon, (diameter, temperature and myelination), it is axon myelination that is the most

significant. This is mainly because axon diameter and body temperature are kept fairly

constant.

The degenerative disease multiple sclerosis is due to the destruction of the myelin sheath

on somatic motor neurons that control skeletal muscle movement. Initially it causes a

slowing of the signal and eventually it can stop motor signals to skeletal muscle all

together. The sensory neurons that are bringing in sensory information are not affected by

multiple sclerosis. So, you could feel your legs normally but would have problems sending

signals out for muscle control.

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3. COMPARISON OF GRADED AND ACTION

POTENTIALS

Below is a side-by-side comparison of graded and action potentials.

Graded Potentials Action Potentials

1) Magnitude varies 1) No variation - All or None

2) Decremental (passive spread) 2) Non-decremental (self-regenerating)

3) No Refractory Periods 3) Two Refractory Periods (absolute

and relative)

4) Summation is possible 4) No Summation possible

5) Trigger: NT's, hormones, etc. 5) Trigger: Threshold reached

6) Occurs at cell body (direction can vary) 6) Occurs at axon hillock (one way

direction)

REFERENCES

1. Hall, John E., and Arthur C. Guyton., (2006). The Textbook of Medical Physiology.11e. Philadelphia, PA: Saunders Elsevier. Pp-58-67.

2. Hille, B., (2001). Ion Channels of Excitable Membranes (3rd Ed.). Sunderland, Massachusetts: Sinauer. pp. 169–200.

3. Vander, A. J., Luciano, D., Sherman, J., (2001). Human Physiology: The Mechanisms of Body Function, 8th Ed. McGraw-Hill Higher Education, Boston, MA, pp. 188-190.

4. Wright, S. H.,(2004) “Generation of resting membrane potential “ Advances in Physiology Education, 28(1–4): 139–142,

5. Barnett, M. W., Larkman, P.M., Larkman, (2007). "The action potential". Pract Neurol 7 (3): 192–197.

6. Stevens, C.F., (1966). Neurophysiology: A Primer. New York: John Wiley and Sons. pp. 127-128.

7. Bullock, T. H., Orkand, R., Grinnell, A., (1977). Introduction to Nervous Systems. A series of books in biology. San Francisco: W. H. Freeman. pp. 160-164.

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