ACTION POTENTIAL
A neuron, has four main parts. The dendrites receive information. The cell body
processes and integrates that information. The axon carries the information along
long distances from one part of the neuron to another. And the axon terminal
transmits the information to the next cell in the chain. A bundle of axons traveling
together is called a nerve. Nerves can be very long, as they often need to transmit
information over long distances. As we just saw, the dendrites are the part of the
neuron that receives incoming signals. Based on the strength of this incoming
stimulation, the neuron must decide whether to pass that signal along or not. If the
stimulation is strong enough, the signal is transmitted along the entire length of the
axon in a phenomenon called an action potential. When this happens, we say the
neuron fires. Transmission of a neuronal signal is entirely dependent on the
movement of ions, or charged particles. Various ions, including sodium, potassium,
and chloride, are unequally distributed between the inside and the outside of the cell.
The presence and movement of these ions is not only important when a neuron fires
but also at rest. To start, let's think about the positively-charged sodium and
potassium ions. When a neuron is not sending a signal, it is considered to be at rest.
In a typical neuron in its resting state, the concentration of sodium ions is higher
outside the cell than inside. The relative concentration of potassium ions is the
opposite, with more ions inside the cell than outside. This ionic separation occurs
right at the cell membrane and creates a chemical gradient across the membrane.
Because ions are charged particles, we also need to consider their charge when
thinking about their distribution across the membrane.
At rest, there are more positively charged ions outside the cell relative to the inside.
This creates a difference in charge across the membrane, which is called an electrical
gradient. Together with the chemical gradient we already mentioned, we refer to this
ionic imbalance as the electrochemical gradient. The difference in total charge
inside and outside of the cell is called the membrane potential. At rest, when no
signals are being transmitted, neuronal membrane has a resting potential of
approximately minus 70 millivolts. This means that the inside of the cell is
approximately 70 millivolts less positive than the outside. Both the chemical and
electrical gradients we just discussed contribute to establishing this potential. While
the inside of the cell has a net negative charge and the outside of the cell has a net
positive charge, the charges line up at the membrane. And the bulk solution on either
side is actually electrically neutral. The resting-membrane potential is the point
where the cell has achieved electrochemical equilibrium.
This means that the concentration gradient and the electro gradient for each ion is
equal and opposite. Ions cannot simply move across the membrane at will. Instead,
they need a protein embedded in the membrane to facilitate their movement. Most
ions cross the membrane through a structure called an ion channel. Ions move
through channels by passive diffusion along their concentration gradient. Some ion
channels are always open, but many require signal to tell them to open or close. For
example, voltage-gated channels only open when the membrane potential reaches a
certain value. On the other hand, ligand-gated ion channels are triggered to open
when they are bound by a specific molecule. Mechanically-gated ion channels open
in response to physical forces, such as changes in length or changes in pressure. Most
ion channels are selectively permeable, meaning that they only allow one, or a small
subset of ions, to pass through. Voltage-gated ion channels, for example, typically
only allow a single ion to cross the membrane when they open. This means that we
need separate channels for each ion, i.e.voltage-gated sodium channels, as well as
voltage-gated potassium channels. As ions move through a channel and cross from
one side of the cell membrane to the other, they cause the membrane potential of the
cell to move away from its resting potential.
If the resulting change in membrane potential is small, we call this a graded potential.
Graded potentials can vary in size, can be either positive or negative, are transient,
and typically do not result from the opening of voltage-gated ion channels. When
ion channels open and a graded potential occurs, the neuron moves quickly to reset
its membrane potential to resting values. This is accomplished primarily by the use
of the sodium-potassium pump, which uses the energy generated by ATP hydrolysis,
to actively transport ions across the membrane against their concentration gradient.
In other words, sodium is transported to the outside of the cell, where its
concentration is higher, and potassium is transported back into the cell, where its
concentration is higher. One cycle of this pump transports three sodium ions outside
the cell and brings two potassium ions inside the cell. This unbalanced charge
transfer contributes to the separation of charge across the membrane and also to the
ionic concentrations we see at rest, thus, restoring the chemical and electrical
gradients to their resting levels. Maintaining these ionic balance in neurons is so
important that this process can account for 20% to 40% of the brain's total energy
use. Only when the resting membrane potential and ion distributions are maintained
at precise levels, will the neuron be poised and ready to fire an action potential.
When the outside stimulation is large enough to bring the membrane potential in the
neuron body up from minus 70 millivolts to the threshold voltage of minus 55
millivolts or higher, this triggers an action potential at the axon hillock, which then
travels down the axon. Voltage-gated sodium channels have three states--open,
closed, and inactivated. At rest, the sodium channel is closed. Once the cell
membrane reaches the threshold voltage, the channel changes to an open position
and sodium rushes into the cell because of the electrochemical gradient. As positive-
sodium ions enter the cell, the membrane potential becomes less negative and more
positive as it approaches 0 millivolts. This is called depolarization.
Eventually, the voltage gradient goes to zero and beyond 0 up to a positive 30
millivolts. This is called an overshoot. As the membrane potential becomes positive,
the sodium channel inactivation gate shuts, making the channel inactivated. This
stops the flow of sodium ions into the cell. The change in membrane potential also
opens the voltage-gated potassium channels, though they open and close more
slowly. Because of the potassium-electrochemical gradient, potassium ions flow out
of the cell, making it less positive and eventually negative. This process is called
repolarization.
Because the potassium channels are a little slow to close, for a brief period, the
membrane potential is hyperpolarized. It's more negative than the resting potential.
During hyper-polarization, the potassium channels close. Throughout all of this, the
sodium-potassium pump is still working. The pump restores the chemical gradients
by putting the sodium and potassium back in place. And the pump re-establishes the
potential gradient by moving more sodium ions out than potassium ions in. This
returns the membrane potential back to its resting potential. During repolarization,
the inactivated sodium channels won't respond to any stimulus at all.
During this time, the neuron is in its absolute refractory period, the period of time
when a nerve cannot fire another action potential, no matter how strongly it's
stimulated. The absolute refractory period prevents action potentials from happening
again too quickly and prevents action potential from traveling backwards along the
axon. During hyperpolarization the sodium channels are closed and the inactivation
gate opens. There is no change in sodium flow, but now they could be opened again.
This is called the relative-refractory period. Because, while the sodium channels
could open, it would take a larger than usual stimulus to reach threshold, because the
cell is hyperpolarized due to the potassium still leaving the cell. The amplitude of
the action potential for a particular neuron, that is, the maximum voltage in one
neuron during an action potential, never changes. An action potential doesn't get
bigger with a bigger stimulus. It's all or nothing. It either happens, or it doesn't
happen.
What can change is the frequency of the action potential. A neuron might fire many
more times per second in response to, say, an intense pain and less frequently in
response to a gentle breeze. Some axons transmit action potentials faster than others.
One variable that increases conduction velocity is the presence of myelin sheaths
around axons. Myelin speeds up transmission through a process called saltatory
conduction, in which the action potential signal appears to jump along the part of the
axon covered by the sheath. In the peripheral nervous system, the sheaths are formed
from glial cells known as Schwann cells. There are small gaps between Schwann
cells called the nodes of Ranvier. The action potential appears to jump from node to
node, speeding the transmission. In the central nervous system, the sheets are made
by cells known as oligodendrocytes. To review, with no stimulus, the membrane is
at its resting potential. A small stimulus causes a graded potential. And a stimulus
above the threshold creates an action potential, and the neuron fires.