Neurons are specialized cells that transmit information. Within the nervous system, they
are arranged into complex networks of circuits that enable our thoughts, sensations, and actions.
Neurons transmit information through two different molecular processes. In the first of these
processes, a signal is passed from cell to cell via chemical messengers called neurotransmitters.
This occurs at synapse, the convergence point of two neurons. One neuron releases neurotransmitters
from storage vesicles into the synaptic cleft a small gap separating the two neurons.
There are many types of neurotransmitters that carry different types of signals.
For example, the neurotransmitter glutamate is an agent in pain signaling,
among many other pathways. As shown here, glutamate binds to its receptor,
causing the receptor to open its ion channel and allow ions to enter the neuron.
This ionic influx initiates the second signaling process that neurons
employ — the action potential. To understand how these ions initiate the action potential,
we need to examine the neuronal membrane when the neuron is at rest. In the resting state, various
types of ions surround the membrane. Outside the neuron, the dominant ion type is sodium,
while inside, the dominant ion type is potassium — both are positively charged.
This unbalanced ionic distribution forms concentration gradients across the membrane.
Neurons establish and maintain these gradients largely by the sodium-potassium pump,
a membrane protein that pumps three sodium ions out of the neuron
for every two potassium ions that it pumps in.
But there is one other kind of gradient here — a gradient of charge. The positive charges
on the outside are balanced to some degree by the chloride ions. On the inside, the
positive charges are balanced to a better degree by the net negative charges of cellular proteins.
This creates a positive charge on the outside of the neuron relative to the inside. We call
this difference in charge across the membrane a voltage. In neurons, voltage-gated ion channels
act as gatekeepers for ion traffic across the membrane. Thanks to their voltage-sensing
domains, these channels open and close in response to changes in membrane voltage.
Remember that influx of ions we saw earlier? It causes a change in the voltage! Voltage-gated
sodium channels sense this change and open, allowing sodium ions into the neuron. These
sodium ions are flowing down gradients of both concentration and charge. Their influx triggers
more sodium channels to open, creating a positive feedback loop as neighboring sodium channels
activate one another. This process of continuous amplification is called an action potential.
To prepare for the next action potential the neuron must terminate the signal. This occurs in
four steps. At a critical point the sodium channels close and become temporarily
inactivated blocking further sodium ion entry. Meanwhile the voltage-gated potassium channels
offset the change in voltage by opening and allowing potassium ions to exit the neuron.
Concurrently, the sodium-potassium pump restores the original ionic gradients,
pumping sodium out and potassium in in a three-to-two ratio.
Finally, after a short refractory period, the sodium channels reopen their inactivation gates
and become ready for the next action potential.
Once the action potential reaches the end of the axon,
it stimulates neurotransmitter release propagating the signal onto the next neuron.
Neurotransmitter release depends on the presence of calcium ions which are abundant outside the
neuron but sparse inside. The action potential triggers voltage-gated calcium channels to open
allowing an influx of calcium ions. These calcium ions then activate special proteins
that mediate the fusing of vesicles with the membrane. The vesicles release their
neurotransmitters into the synaptic cleft which diffuse across and start the signaling cycle anew
Together neurotransmitters, gradients, ion channels, and ion pumps
work in harmony to create the neuronal signaling symphony.