Biochemistry of Methamphetamine

Neurotransmission

What are neurons?

These as special cells in your brain that receive, conduct, and transmit messages in the form of chemicals between one another. It is an enormously complex system. The neurons that are interconnected in the CNS communicate with one another by releasing signaling chemicals called neurotransmitters at the small gaps between two neurons (synaptic cleft).


What makes up a neuron?

There are three basic parts in a neuron: soma, axon, and dendrites. The soma is the cell body that contains the nucleus and many of the organelles found in other types of cells (ribosomes, chromosomes, Golgi apparatus, etc, but no centrioles). The axon is a single long tube that extends from the soma with multiple branchings at the end of it. The main function of the axon is to carry a message from the soma to the terminal buttons, which are the structures at the end of the axon that release the neurotransmitters into the synaptic cleft. The dendrites are the smaller tree-like branchings that project from the soma. Their chief function is to receive the signals from the axons of other neurons.

At this point, you may have noticed that neurotransmitters play an important role in the workings of a neuron. The basic message that is transmitted is called the action potential. It is an electrochemical impulse that travels down the axon (from the soma toward the terminal buttons) at about a speed of 100m/sec.


How is the action potential produced?

All cellular membranes are electrically charged due to the concentration of ions present in the extracellular and intracellular space. For neurons, sodium ions (Na+) and chlorine ions (Cl+) exists in large quantities in the extracellular space while the intracellular space contains many potassium ions (K+) and other organic anions (A+). The cell membrane contains ion channels that regulate the passing of these various ions between the inside and outside of the cell. When the cell is at the resting potential (-70mV), the intracellular space is more negative relative to the extracellular space and the voltage-dependent Na+ and K+ channels are closed (see picture below).

The opening of Na+ channels is triggered by the reduction of the membrane potential (depolarization) to the threshold of excitation. Once the ion channels open, the action potential begins as electrostatic pressure and the force of diffusion drive Na+ into the cell. The entry of positively-charged ions into the cell actually reverses the electrical potential from a negative potential to a positive one, (i.e., the inside becomes positive). This depolarization is produced by the entry of Na+, which subsequently causes the K+ channels to open. The force of diffusion drives K+ out of the cell. In about 1 millisecond, the membrane potential reaches +40mV because of the many Na+ ions entering the cell.

The entry of positively charged ions into the cell reduces the membrane potential to an extent that causes the inside to become positive. The depolarization caused by the entry of Na+ causes the K+ channels to open and the force of diffusion drives K+ out of the cell. In about 1 millisecond, the membrane potential reaches +40mV because of the Na+ entering the cell. At this point, the Na+ channels become blocked (refractory) and Na+ cannot enter the cell anymore. But the K+ channels remain open and are continually pumping K+ out of the cell. The outflow of K+ helps to bring the membrane potential back to its resting value. Once the resting potential is reached, the K+ channels close.

Once the membrane potential reaches +40mV, the Na+ channels become blocked and Na+ cannot enter the cell anymore. But the K+ channels remain open and continually pump K+ out of the cell. The outflow of K+ helps to bring the membrane potential back to its resting value. Once the resting potential is reached, the K+ channels close. As you can see from picture below, the membrane actually overshoots the resting potential (hyperpolarization) and there is an excess of K+ outside of the membrane. The resting potential returns to -70mV as the excess K+ diffuses away (repolarization).


How does the action potential trigger the release of neurotransmitters?

The action potential begins at the end of the axon that is attached to the soma and travels down toward the terminal buttons. Terminal buttons contains synaptic vesicles that store neurotransmitters after they are synthesized. The neuron transmitting the message is called the presynaptic neuron. The neuron receiving the message is called the postsynaptic neuron. The neurotransmitters released from the presynaptic neuron transmit a message to the dendrites of the postsynaptic neuron. When the action potential reaches the terminal buttons, the depolarization causes voltage-dependent calcium (Ca2+) channels on the presynaptic membrane to open and allows Ca2+ to enter into the cell. Ca2+ binds with the membrane of the synaptic vesicles, which causes the vesicles to break and release the neurotransmitter into the synaptic cleft.


What happens after the neurotransmitters are released?

After the neurotransmitters are released, they diffuse across the synaptic cleft and interact with receptors on the postsynaptic membrane. The neurotransmitters attach to binding sites on the postsynaptic receptors and initiate the opening of neurotransmitter-dependent ion channels. This allows the passage of ions into or out of the cell. The neurotransmitters in the synaptic cleft serve an important purpose, which is to permit ions to pass through the postsynaptic membrane and produce postsynaptic potentials. There are two types of postsynaptic potentials, excitatory (EPSP) or inhibitory (IPSP). Producing an EPSP or IPSP in the postsynaptic neuron depends on the specific type of ion channel that is activated by the receptors. If the movement of ions (i.e., Na+ into the cell) causes a depolarization of the postsynaptic neuron, it will result in an EPSP. If the movement of ions (i.e., K+ out of the cell) produces a hyperpolarization and the membrane becomes more negative, resulting in an IPSP.

The postsynaptic potentials produced by all neurotransmitters are brief and terminated by reuptake. Dopamine, serotonin, and norepinephrine produce postsynaptic potentials that are terminated by reuptake. Reuptake is a process that removes the neurotransmitters in the synaptic cleft. The presynaptic membrane contains special transporter molecules that move neurotransmitters from the synaptic cleft directly into the cytoplasm. So an action potential causes the terminal buttons to release a small amount of neurotransmitters into the synaptic cleft and quickly takes it back.


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Introduction

Neurotransmitters

Dopamine

Serotonin

Norepinephrine