Neuronal Signaling

Introduction

The purpose of the nervous system is to transfer information from the PNS to the CNS, process the information in the CNS, and send back information to the PNS. This transfer of information from the external environment, through neurons, and back again to the external environment is known as neuronal signaling.

A summary of neuronal signaling:

Before a neuron receives a signal, it is in a resting state
Neurons receive signals in two forms:

Chemical changes. This is done via neurotransmitters (see Synaptic Transmission below) or chemical elements in the environment (e.g., olfactory receptors)
Physical changes. Examples include touch receptors in the skin or photoreceptors in the retina

These signals cause ionic fluctuations in the neuron’s plasma membrane which creates an electrical current flow in the neuron
This current flow travels down the axon (perhaps long-distance through action potential, explained below)
When the current reaches the terminal boutons, neurotransmitters are released to other neurons or the environment

Membrane Potential

Diffusion

	Example where the concentration of an ion is 100% on one side of the membrane (blue line) and 0% on the other. This imbalance is maintained because the membrane is impermeable to that ion.
	Here the ions have diffused across the membrane because it has become permeable to that ion (dotted black line) and the concentration on either side is 50/50. Equilibrium has been reached.

Ions want to move from a high concentration to a low concentration in order to create equilibrium.

If there is an imbalance across the membrane, then there is a concentration gradient (CG) across the membrane

Selective Permeability

	Here two kinds of ions are displayed. The membrane is impermeable to both.
	This membrane is permeable to only one kind of ion, but is impermeable to the other. The member is therefore selectively permeable to one kind of ion. Here the selectivity is based on size, however, other facts may influence permeability.

Electrostatic Pressure

Ions of like charges repel (positive with positive or negative with negative), and of opposite charges attract (positive with negative or negative with positive)

If there is a difference in charges across the membrane, then there is an electrical potential across the membrane

For example, positively charged ions in the extracellular space will be attracted toward a negatively charged intracellular fluid. Only the neuron's membrane could keep them apart

Neuron’s Resting State

In its resting state, an electrical gradient is maintained across the neuron’s membrane, thereby creating a resting membrane potential. This section explains how this is maintained.

Properties of neuronal membrane:

The neuron’s membrane forms a separation between the extracellular space around the neuron and its intracellular fluid

The membrane is mostly impermeable, forming a barrier to many proteins, molecules, and other ions dissolved in the intracellular and extracellular fluids

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⁺.

The membrane is responsible for maintaining the neuron’s membrane resting potential. This is defined as the voltage difference between the extracellular and intracellular spaces. This voltage difference is between –60 and –80 millivolts, but on average –70 mV

This transforms a neuron into the equivalent of a battery, allowing them to generate electrical signals

Reasons for a membrane’s resting potential:

Sodium-Potassium Pump

The membrane has protein (or enzyme) channels, or gaps, which forms a transmembrane pump.

These pumps use energy-storing molecules called adenosine triphosphate (ATP)

ATP actively pumps 3 Na⁺ ions out of the cell, at the same time pumping 2 K⁺ into the cell.

After a while, a ionic concentration gradient is generated across the membrane, whereby more Na⁺ ions are outside and more K⁺ are inside

Because of diffusion, the tendency is for Na⁺ ions to travel back to the inside, and vice versa for K⁺ ions

There are nongated channels in the membrane that permit the passage of some Na⁺ ions back into the neuron, and K⁺ ions out of the neuron (again, using diffusion to achieve a concentration equilibrium), however, the membrane is not very permeable to Na⁺ ions. Hence many more K⁺ ions leave the cell than Na⁺ ions enter. This causes an excess of negative charge in the cell.

The K⁺ ions continue to leak out until there is an equilibrium reached between the concentration gradient and the electric potential (i.e., the attraction of K⁺ positive ions back to the negatively charged intracellular fluid)

The voltage differential, again, is –70 mV on average

Neuronal Stimulation

A number of factors contribute to a neuron’s stimulation, which causes a change in the neural membrane’s permeability

Mechano-sensitive channels are affected by distortions or deformations in the membrane around it

Voltage-sensitive channels are affected by the current voltage around the membrane

Ligand-sensitive channels are affected by chemical agents (found on dendrites and postsynaptic cells)

Passive Potential

The moment a neuron’s membrane is affected by some stimuli, the following happens:

A chemical or physical change causes some Na⁺ ion channels in the membrane to open temporarily
Na⁺ ions enter the cell because of the concentration gradient and electrostatic pressure, making the inside of the cell more positive (depolarization)
Because of this electrical change, the K⁺ ions are pushed out through the non-gated K⁺ ion channels
The current spreads passively as adjacent parts of the membrane also become depolarized
The current is proportional to the size of the simulation, but passive potentials decay with time and distance from the source of the depolarization

As long as the simulation does not cause a depolarization of more than 15 to 20 mV (-50 mV is the treshhold for an action potential), the electric current generated decays with distance and time, and is generally restricted to the area stimulated

The cell eventually returns to its resting state

This form of neuronal signaling is only effective over short distances. For example, neurons in the retina use passive potential to communicate with one another

Action Potential

As long as the stimuli does not cause the membrane potential to reach -50 mV, only a passive current that diminishes with time and distance is generated through the neuron. However, if the stimuli is enlarged or additional 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 to the size of the simuli).

A. Depolarization

If a passive potential depolarizes the membrane to about -50 mV, all Na⁺ voltage-gated channels are opened:

A combination of diffusion and electrostatic pressure causes a sudden rushing in, or influx, of Na⁺ ions into the neuron's intracellular fluid
This causes a further depolarization of the membrane, and more Na⁺ voltage-gated channels are opened
This is a rapid self-reinforcing cycle (which lasts about 25ms) that continues until all Na⁺ voltage-gated channels are opened. It is known as the Hodgkin-Huxley Cycle

Because the membrane has suddenly become 100% permeable, its membrane potential becomes very positive inside the neuron, about +50 mV.

This massive depolarization is digital, i.e. all or none, and is independent of the stimulation intensity

B. Absolute Refractory Period

The moment the membrane potential hits +50 mV, all the Na⁺ voltage-gated channels are closed and the K⁺ voltage-gated channels are opened:

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⁺ voltage-gated channels are opened to the time when the K⁺ voltage-gated channels are closed again, is called the absolute refractory period

During the absolute refractory period no further action potential can occur:

The Na⁺ voltage-gated channels are completely closed
Hence the membrane cannot be depolarizated with an influx of Na⁺ ions

C. Relative Refractory Period

After the absolute refractory period, there is a period when both Na⁺ and K⁺ voltage-gated channels remain closed:

This causes the membrane potential to be even more negative than at rest
The membrane potential is now hyperpolarized ("hyper" means extra, super)
It would take more stimuli to bring the potential to threshold in order to create another action potential
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 stimulus intensity	Always the same size
Stimulation	Requires very little	Requires a 15-20 mV change
Summation	Adds the stimuli strengths	Only one potential at a time
Spread	Decay with distance	Actively regenerated
Duration	As long as the stimulus	Constant duration
Main channels used	Non-gated channels	Voltage-gated channels

Passive Conduction

Both passive potentials and active potentials propagate current in the intracellular fluid of the neuron.

The passive potential operates like a graded analog signal
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 how much current leaks out
The conductivity of the axon is dependent on its diameter size (the larger the better)

For most neurons, passive conduction is not good enough to conduct the current signal all the way down the axon to the terminal boutons.
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 to conduct the current signal very far. Axons therefore provide a method, called active conduction, to maintain the current with undiminished intensity by way of repeated action potentials. There are two forms of active conduction:

Unmyelinated Axons

Axons without myelin sheaths surrounding them use many voltage gated Na⁺ channels in proximity to one another
An action potential depolarizes the surrounding area by the passive conduction of the depolarizing current
The nearby Na⁺ channels then open, which generates another action potential
This process is repeated until the action potential reaches the terminal boutons
Note: the action potential cannot travel backwards because of the refractory period

Myelinated Axons

Rather than having many Na⁺ channels in close proximity, axons also use a myelin sheath (in the form of Schwann cells in the PNS or oligodendrocytes in the CNS) to increase action potential speed
The myelin around the axon prevents current leakage by increasing resistance in the axon
The passive current therefore spreads further down the axon, until it reaches the gaps between the myelin sheaths (Nodes of Ranvier)
The Nodes of Ranvier contains Na⁺ channels, which fire another action potential upon depolarization from the passive current
This 'jumping' of action potentials from node to node is called saltatory conduction

Note: as before, the action potential cannot travel backwards due to the refractory period