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7/29/2019 Neuronal Signaling
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Neuronal Signaling
Introduction
The purpose of the nervous system is to transfer information from the PNSto the CNS, process the information in the CNS, and send back informationto the PNS. This transfer of information from the external environment,through neurons, and back again to the external environment is known asneuronal signaling.
A summary of neuronal signaling:
• Before a neuron receives a signal, it is in a resting state• Neurons receive signals in two forms:
o Chemical changes. This is done via neurotransmitters (see
Synaptic Transmission below) or chemical elements in theenvironment (e.g., olfactory receptors)
o Physical changes. Examples include touch receptors in theskin or photoreceptors in the retina
• These signals cause ionic fluctuations in the neuron’s plasmamembrane which creates an electrical current flow in the neuron
• This current flow travels down the axon (perhaps long-distancethrough action potential, explained below)
• When the current reaches the terminal boutons, neurotransmittersare released to other neurons or the environment
Membrane Potential
•
Diffusion
Example where the concentration of an ionis 100% on one side of the membrane (blueline) and 0% on the other. This imbalance ismaintained because the membrane isimpermeable to that ion.
Here the ions have diffused across themembrane because it has becomepermeable to that ion (dotted black line)and the concentration on either side is50/50. Equilibrium has been reached.
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o Ions want to move from a high concentration to a lowconcentration in order to create equilibrium.
o If there is an imbalance across the membrane, then there is aconcentration gradient (CG) across the membrane
• Selective Permeability
Here two kinds of ions are displayed. Themembrane is impermeable to both.
This membrane is permeable to only onekind of ion, but is impermeable to theother. The member is therefore selectivelypermeable to one kind of ion. Here theselectivity is based on size, however, otherfacts may influence permeability.
• Electrostatic Pressure
o Ions of like charges repel (positive with positive or negative
with negative), and of opposite charges attract (positive withnegative or negative with positive)o If there is a difference in charges across the membrane, then
there is an electrical potential across the membraneo For example, positively charged ions in the extracellular space
will be attracted toward a negatively charged intracellularfluid. Only the neuron's
membrane could keep them apart
Neuron’s Resting State
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In its resting state, an electrical gradient is maintained across theneuron’s membrane, thereby creating a resting membrane potential. Thissection explains how this is maintained.
• Properties of neuronal membrane:
o The neuron’s membrane forms a separation between theextracellular space around the neuron and its intracellularfluid
o The membrane is mostly impermeable, forming a barrier tomany proteins, molecules, and other ions dissolved in theintracellular and extracellular fluids
o It is selectively permeable to only a few ions, notably sodium(Na+), potassium (K +), and chlorine (Cl-)
However, the membrane is not equally permeable to all:K +>Cl->>>Na+, i.e., it is most permeable to K +, less to
Cl-
, and a lot less to Na+
.o The membrane is responsible for maintaining the neuron’s
membrane resting potential. This is defined as the voltagedifference between the extracellular and intracellular spaces. This voltage difference is between –60 and –80 millivolts, buton average –70 mV
o This transforms a neuron into the equivalent of a battery,allowing them to generate electrical signals
• Reasons for a membrane’s resting potential:o Sodium-Potassium Pump
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o The membrane has protein (or enzyme)
channels, or gaps, which forms a transmembranepump.o These pumps use energy-storing moleculescalled adenosine triphosphate (ATP)o ATP actively pumps 3 Na+ ions out of thecell, at the same time pumping 2 K + into the cell.
o After a while, a ionic concentration gradient is generatedacross the membrane, whereby more Na+ ions are outside andmore K + are inside
o Because of diffusion, the tendency is for Na+ ions to travelback to the inside, and vice versa for K + ions
o There are nongated channels in the membrane that permitthe passage of some Na+ ions back into the neuron, and K +
ions out of the neuron (again, using diffusion to achieve aconcentration equilibrium), however, the membrane is notvery permeable to Na+ ions. Hence many more K + ions leavethe cell than Na+ ions enter. This causes an excess of negativecharge in the cell.
o The K + ions continue to leak out until there is an equilibriumreached between the concentration gradient and the electricpotential (i.e., the attraction of K + positive ions back to the
negatively charged intracellular fluid)o The voltage differential, again, is –70 mV on average
Neuronal Stimulation
A number of factors contribute to a neuron’s stimulation, which causes achange in the neural membrane’s permeability
• Mechano-sensitive channels are affected by distortions ordeformations in the membrane around it
• Voltage-sensitive channels are affected by the current voltage
around the membrane
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• Ligand-sensitive channels are affected by chemical agents (found ondendrites and postsynaptic cells)
Passive Potential
The moment a neuron’s membrane is affected by some stimuli, thefollowing happens:
o A chemical or physical change causes some Na+ ion channelsin the membrane to open temporarily
o Na+ ions enter the cell because of the concentration gradientand electrostatic pressure, making the inside of the cell morepositive (depolarization)
o Because of this electrical change, the K + ions are pushed outthrough the non-gated K + ion channels
o
The current spreads passively as adjacent parts of themembrane also become depolarizedo The current is proportional to the size of the simulation, but
passive potentials decay with time and distance from thesource of the depolarization
o As long as the simulation does not cause a depolarization of more than 15 to 20 mV (-50 mV is the treshhold for an actionpotential), the electric current generated decays with distanceand time, and is generally restricted to the area stimulated
o The cell eventually returns to its resting stateo This form of neuronal signaling is only effective over short
distances. For example, neurons in the retina use passivepotential to communicate with one another
Action Potential
As long as the stimuli does not cause the membrane potential to reach -50mV, only a passive current that diminishes with time and distance isgenerated through the neuron. However, if the stimuli is enlarged oradditional stimuli is provided to the cell, a depolarization of more than 15
to 20 mV may occur (this is possible because the current is proportional tothe size of the simuli).
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A. Depolarization
If a passive potential depolarizes the membrane to about -50mV, all Na+ voltage-gated channels are opened:
o A combination of diffusion and electrostaticpressure causes a sudden rushing in, or influx , of Na+ ions into the neuron's intracellular fluido This causes a further depolarization of themembrane, and more Na+ voltage-gated channelsare openedo This is a rapid self-reinforcing cycle (whichlasts about 25ms) that continues until all Na+
voltage-gated channels are opened. It is known asthe Hodgkin-Huxley Cycle
o Because the membrane has suddenlybecome 100% permeable, its membrane potentialbecomes very positive inside the neuron, about+50 mV.o This massive depolarization is digital, i.e. all
or none, and is independent of the stimulationintensity
B. Absolute Refractory Period
The moment the membrane potential hits +50 mV, all the Na+
voltage-gated channels are closed and the K + voltage-gatedchannels are opened:
o This causes K + ions to flow out, or efflux , of the neuron, thereby causing a repolarization of
the membrane. This period from the time the Na+
voltage-gated channels are closed and the K +
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voltage-gated channels are opened to the timewhen the K + voltage-gated channels are closedagain, is called the absolute refractory periodo During the absolute refractory period nofurther action potential can occur:
The Na+ voltage-gated channels arecompletely closed Hence the membrane cannot bedepolarizated with an influx of Na+ ions
C. Relative Refractory Period
After the absolute refractory period, there is a period whenboth Na+ and K + voltage-gated channels remain closed:
o This causes the membrane potential to beeven more negative than at resto The membrane potential is nowhyperpolarized ("hyper" means extra, super)o It would take more stimuli to bring thepotential to threshold in order to create anotheraction potentialo This period is called the relative refractory period
Sections A, B, and C above are depicted graphically in the
diagram below:
Comparison Between Passive Potential and Active Potential
Description Passive Potential Active Potential
Amplitude Graded with stimulusintensity
Always the same size
Stimulation Requires very little Requires a 15-20 mV
change
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Summation Adds the stimulistrengths
Only one potential at atime
Spread Decay with distance Actively regenerated
Duration As long as the stimulus Constant duration
Main channelsused
Non-gated channels Voltage-gated channels
Passive Conduction
Both passive potentials and active potentials propagate current in theintracellular fluid of the neuron.
o The passive potential operates like a graded analog signalo It decays with time and distance:
The original intensity of the stimulus affects the size of the depolarizing current
The resistance of the membrane contributes to howmuch current leaks out
The conductivity of the axon is dependent on itsdiameter size (the larger the better)
o For most neurons, passive conduction is not good enough toconduct the current signal all the way down the axon to the
terminal boutons.o Another method is therefore needed to conduct a current
signal down longer axons: active conduction.
Active Conduction
Because the action potential's depolarization is localized, it is not able toconduct the current signal very far. Axons therefore provide a method,called active conduction, to maintain the current with undiminishedintensity by way of repeated action potentials. There are two forms of active conduction:
Unmyelinated Axons
o Axons without myelin sheaths surrounding them use manyvoltage gated Na+ channels in proximity to one another
o An action potential depolarizes the surrounding area by thepassive conduction of the depolarizing current
o The nearby Na+ channels then open, which generates anotheraction potential
o This process is repeated until the action potential reaches the
terminal boutons
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o Note: the action potential cannot travel backwards because of the refractory period
Myelinated Axons
o Rather than having many Na+ channels in close proximity,axons also use a myelin sheath (in the form of Schwann cellsin the PNS or oligodendrocytes in the CNS) to increase actionpotential speed
o The myelin around the axon prevents current leakage byincreasing resistance in the axon
o The passive current therefore spreads further down the axon,until it reaches the gaps between the myelin sheaths (Nodesof Ranvier)
o The Nodes of Ranvier contains Na+ channels, which fireanother action potential upon depolarization from the passivecurrent
o This 'jumping' of action potentials from node to node is calledsaltatory conduction
o Note: as before, the action potential cannot travel backwardsdue to the refractory period