Release of Neurotransmitter

Conduction of the Depolarization to the Presynaptic Terminals by Action Potentials

In an afferent neuron, the receptor potential is a depolarization caused by the opening of ion channels that are gated by the sensory stimulus. These ion channels are only found in the sensory dendrites where the sensory stimulus is applied. In a touch afferent, for example, the ion channels are mechanically gated.

When a receptor potential is created in the sensory dendrites, it tends to conduct a short distance down the axon since the core of the axon is a solution of ions. But the axon is a "leaky"" conductor of electricity and the receptor potential only conducts a few millimeters. To conduct the information into the central nervous system, entirely different ion channels in the axon create the action potential which travels as a wave along the axon.

Two types of ion channels create the axon potential. Both are voltage gated, with membrane depolarization in both cases causing the ion channels to open.

The first ion channels to open are the voltage gated Na+ channels. These begin to open rapidly once the membrane potential surpasses the threshold. Indeed, the threshold is determined by the membrane potential at which voltage gated Na+ ion channels open.

QUESTION: Once the threshold is surpassed, how does the opening of voltage gated Na+ create positive feedback?


QUESTION: Why is an action potential an "all-or-nothing" pulse of one size?


The K+ channels also open with depolarization, but they open more slowly. As a result, the K+ channels do not open until the Na+ channels are almost all open and the action potential has reached it peak.

QUESTION: Why is the opening of the K+ channels negative feedback?


QUESTION: What causes the voltage gated Na+ and voltage gated K+ channels to close?


Presynaptic Release of Neurotransmitter

Eventually, the action potential conducts to all the presynaptic terminals at the ends of the branches of the axon. Each presynaptic terminal contains many synaptic vesicles, which are filled with neurotransmitter. At any given time, a number of these vesicles are docked at the release zone at the plasma membrane immediately at the synaptic cleft.

Refer to the figure to the right and observe how the v-SNARE and t-SNARE proteins hold these docked vesicles in place. These vesicles are immediately available for release. Indeed, they are so poised for release, that occasionally one will release its contents into the synaptic cleft spontaneously, as will be shown on the next webpage.

When an action potential depolarizes a presynaptic terminal, some of these docked vesicles release their neurotransmitter into the synaptic cleft. The figure to the left shows the first step linking the depolarization of the action potential to the exocytosis of the vesicles. The depolarization causes Ca++ channels in the membrane near the release sites to open. It is this that triggers the exocytosis of the vesicles. The red molecules are postsynaptic receptors in the postsynaptic membrane.

QUESTION: What type of factor gates the Ca++ channels shown in the figure?


QUESTION: What type of factor gates the ion channels shown in the postsynaptic membrane?


The figure to the right shows Ca++ triggering the exocytosis. We are not going to study the specific additional molecules involved. One, for example, binds the Ca++, while others connect the vesicle membrane and plasma membrane and create an initial pore that widens until the exocytosis is complete. The process is extraordinarily rapid. The interval from the entry of Ca++ until the exocytosis of neurotransmitter is less than one millisecond.

The synaptic cleft is extremely narrow, so that the neurotransmitter diffuses to the postsynaptic receptors in the postsynaptic membrane almost instantaneously (about 0.1 msec).

The process of exocytosis adds membrane to the plasma membrane of the presynaptic terminal. Away from the release site, the extra membrane is removed from the plasma membrane by endocytosis. The resulting vesicles then fuse with an endosome.

QUESTION: Can you name two types of toxins that attack the SNARE proteins? (One is described on the handout. The other tends to reduce the release of inhibitory neurotransmitter.)


QUESTION: Surely vesicles are used up quickly. Where do you suppose new vesicles come from?


QUESTION: In some cases a protein is released along with the neurotransmitter. How does that get into the vesicle?


QUESTION: What happens to the neurotransmitter in the synaptic cleft?