The insides of cells are usually negatively charged. Table 6-1 shows the ion concentration inside and outside of cells. When the cell membrane receives a stimulus, positive Na ions leak into the cell and generate a positive charge inside. These positive Na ions are then pumped back out of the cell. At the same time, positive K ions, which are more abundant inside than outside of the cell, leak out of the cell. Pumping out of Na ions and leaking out of K ions from the cell make the intracellular electric potential negative again. This temporary change in the electric potential is called action potential (Fig. 6-7).

Table 6-1. Ion Composition inside and outside the Cell

Fig. 6-7. Action Potential

Fig. 6-8. Release and Recycling of Neurotransmitters

Terminals of neurons contain vesicles that store neurotransmitters. Stimuli are transmitted through axons to their terminals and are released from there. The released substances bind to receptors of adjacent nerves (Fig. 6-8). From there, a new action potential is generated. There are various kinds of neurotransmitters. These include monoamines, such as serotonin (involved in mood and appetite), dopamine (involved in volition and addiction), and noradrenaline. Other neurotransmitters include amino acids (GABA, glycine, glutamic acid, etc.), nucleotides (ATP etc.), gases (nitric oxide, carbon monoxide, etc.), and peptides (oxytocin, substance P, etc.). Glutamic acid is an excitatory neurotransmitter, whereas glycine and GABA are inhibitory neurotransmitters.

Substances in the body (neurotransmitters in this case) that bind to receptors are called ligands (Fig. 6-9). Substances that stimulate receptors in the same manner as ligands are called agonists, while substances that bind to receptors and inactivate them are called antagonists. For example, nicotine is an agonist of the brain's nicotinic acetylcholine receptors (nAchR), which are closely involved in cognition. This is why tobacco clears a smoker's head and increases his or her concentration. The arrow poison curare is an antagonist. Animals shot with a curare-poisoned arrow become paralyzed because curare binds to nAchR in the animal's muscles and prevents their contraction (relaxes them). The activity of drugs is explained by their affinity to this receptor. For example, chlorpromazine, a drug for schizophrenia, is an antagonist of the dopamine D2 receptor. Therefore, it is believed that chlorpromazine may alleviate schizophrenia-positive symptoms because these symptoms are caused by increased activity of dopamine.

Fig. 6-9 Agonists and Antagonists

Ligands have an affinity for receptors in the body and become physiologically active in the cell after binding to them. Agonists are foreign substances whose activity is similar to that of ligands. Antagonists are foreign substances that inhibit ligand's activity.

Neurotransmitters released across the synaptic cleft are either broken down on the spot, diffused through the cell membrane, or vigorously recovered from the previous synapse. For example, acetylcholine is broken down by the enzyme esterase. The inhibitor of esterase is a drug for the treatment of Alzheimer's disease. Furthermore, the gaseous transmitter nitric oxide is transmitted by diffusion, but its range is narrow. Presynaptic membrane proteins called transporters vigorously recover neurotransmitters and allow only specific substances, such as serotonin and dopamine, to pass the membrane. Transporters are not present everywhere in the brain. For example, dopamine transporters are only present in dopamine neurons. The substance MPTP resembles an artificial drug and is absorbed into the nerves from a dopamine transporter. MPTP in the brain kills dopamine nerves exclusively. When people are poisoned by MPTP, their dopamine nerves die and they develop symptoms similar to those of Parkinson's disease.


What Causes Depression?

Depression is accompanied by a decrease in a group of chemicals in the brain called monoamines, which include serotonin, noradrenaline, and dopamine. Iproniazid, which was developed as an antimicrobial agent for tuberculosis, has been reported to improve depression because it suppresses downregulation of monoamines in the brain. It has also been reported that the amount of monoamines also decreases in the cerebrospinal fluid during depression. Lately, serotonin has been attracting the most attention among the monoamines, and drugs that increase serotonin in the brain are attracting attention as drugs for treatment of depression.

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