PROFESSOR: This is a neuron,
which 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 are 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.
