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2.5.2 Neurons and Ions

2.5.2.1 Overview

Neurons play decesive roles of the brain handling signals through ion transfer. The basic mechanism should be learned as follows.

2.5.2.2 Details

2.5.2.2.1 Myelinated Neurons and Electrolytes (Ions)

The neurons discussed hereafter refer specifically to Myelinated neurons. While the sizes of myelinated neurons vary significantly, the following description focuses on a typical example. In the following depiction, a Myelinated neuron is shown in red-purple, simplified for the purpose of explanation.
The largest part is the cell body, also called the soma. Its diameter is approximately 30 μm, and it contains essential elements such as the nucleus. The long fiber extending from the soma is called the axon. The axon is enveloped by several or more lipid-rich, thin sheet-like glial cells that wrap around it to form a structure known as the myelin sheath. Each myelin segment (myeline sheath) is approximately 1 mm long along the axon. There are periodic gaps between these myelin segments (myeline sheath). The gaps are referred to as the Nodes of Ranvier.
The axon transmits signals to the end of the axon. The end of the axon is subdivided into many tips. The tips are called axon terminals or synaptic terminals. The terminals touch other neurons. (in this case, the other neuron is shown in blue-green.)
The branches from the cell body other than the axon are called dendrites. The dendrites have many small protrusions called dendritic spines, where another neuron's axon terminal typically makes a connection. This contact area between the axon terminal and the dendrite is called a synapse.
Dendrites do not necessarily have spines from the beginning; rather, dendritic spines are formed and grow through the repetition of signal transmissions at the synapses. On average, a single neuron has thousands of dendritic spines. Accordingly, a neuron also receives connections from thousands of axon terminals.


Neuron's Deformed Diagram 1
*Attribution: https://en.wikipedia.org/wiki/File:Blausen_0657_MultipolarNeuron.png


Neuron's Deformed Diagram 2
*Attribution: https://en.wikipedia.org/wiki/File:Complete_neuron_cell_diagram_en.svg

A neuron transmits electrical signals from the dendrites and the cell body to the axon terminals (synaptic terminals). As shown in Diagram 1, when the axon terminals of one neuron (red-purple) form a connection with another neuron’s dendrites (blue-green), the sender is called the presynaptic neuron and the receiver is called the postsynaptic neuron.

*Attribution: https://en.wikipedia.org/wiki/File:Action_Potential.gif

The typical type of the synapse is the chemical synapse, while the other is the electrical synapse. Apart from electrical synapses (found in systems like the heart muscle), the brain primarily relies on chemical synapses to transmit signal.


Chemical Synapse
*Attribution: https://en.wikipedia.org/wiki/File:SynapseSchematic_lines.svg

As for the chemical synapse, the axon terminal of the presynaptic neuron holds specific chemical substances called neurotransmitters, such as glutamate. When a signal is transmitted along the presynaptic neuron from the cell body to the axon terminal, these neurotransmitters are released into the synaptic cleft—the space between the axon terminal and the postsynaptic neuron. This transmission typically occurs between the axon terminal and the dendritic spine of the postsynaptic neuron.
The postsynaptic neuron has receptors located on its dendrites, typically at the dendritic spine. When these receptors receive a neurotransmitter like glutamate, Ligand-Gated Ion Channels are activated, initiating signal transmission within the postsynaptic neuron.
To understand this process clearly, one must learn the ionic composition of body fluids. Body fluids refer to the liquids within the human body. In chemistry, some substances, such as ethanol ($\mathrm{CH_3CH_2OH}$), dissolve in water as intact molecules because they have a high affinity for water due to their electrical polarity.
In contrast, other substances, such as acetic acid ($\mathrm{CH_3COOH}$) and sodium chloride ($\mathrm{NaCl}$), dissolve in water by dissociating into electrically positive and negative parts. For example, they divide into $\mathrm{H^{+}}$ and $\mathrm{CH_3COO^{-}}$, or $\mathrm{Na}^{+}$ and $\mathrm{Cl}^{-}$. This occurs due to the relatively weak bonds between their components and the electrical affinity of the resulting ions to polar water molecules. Substances that dissociate into ions with positive or negative charges when dissolved in water are called electrolytes. (In the case of acids like acetic acid, the resulting negative part, such as $\mathrm{CH_3COO^{-}}$, is referred to as an acid anion or the conjugate base.)

* "Anion in Simple Wikipedia" https://simple.wikipedia.org/wiki/Anion
* "Conjugate Acid in Wikipedia" https://en.wikipedia.org/wiki/Conjugate_acid

Body fluids can be categorized into extracellular fluid (ECF) and intracellular fluid (ICF). Intracellular fluid is the fluid within cells, while extracellular fluid is the fluid outside them. The electrolyte composition of the ECF is primarily regulated by the kidneys. The electrolyte composition of the cerebrospinal fluid (CSF), in which neurons are bathed, is quite similar to that of the general extracellular fluid.
The electrolyte composition and equivalent concentrations (mEq/L) of CSF are approximately: $\mathrm{Na}^{+}$ 138 mEq/L, $\mathrm{K}^{+}$ 5 mEq/L, $\mathrm{Ca}^{2+}$ 5 mEq/L, $\mathrm{Mg}^{2+}$ 3 mEq/L, $\mathrm{Cl}^{-}$ 113 mEq/L, $\mathrm{HCO_3^{-}}$ 27 mEq/L, organic acid anions 6 mEq/L, protein anions 2 mEq/L, $\mathrm{HPO_4^{2-}}$ 2 mEq/L, and $\mathrm{SO_4^{2-}}$ 1 mEq/L, and a small amount of other electrolytes (ions).
In contrast, the composition of the intracellular fluid within neurons is approximately: $\mathrm{Na}^{+}$ 14 mEq/L, $\mathrm{K}^{+}$ 140 mEq/L, $\mathrm{Ca}^{2+}$ 0.0002 mEq/L, $\mathrm{Mg}^{2+}$ 2 mEq/L, $\mathrm{Cl}^{-}$ 4 mEq/L, $\mathrm{HCO_3^{-}}$ 10 mEq/L, protein anions 71 mEq/L, $\mathrm{HPO_4^{2-}}$ 70 mEq/L, and $\mathrm{SO_4^{2-}}$ 1 mEq/L, and a small amount of other electrolytes (ions).

* "Equivalent (Chemistry) on Wikipedia" https://en.wikipedia.org/wiki/Equivalent_(chemistry)

The differences in electrolyte concentrations between the extracellular and intracellular fluids are primarily attributed to cell membranes and ion transporters (ion pumps). Consequently, signal transmission in neurons depends on these concentration gradients, as well as voltage-gated and ligand-gated ion channels.

2.5.2.2.2 Electric Potential Difference

Cell surfaces are defined by the cell membrane, which is primarily composed of a phospholipid bilayer. This bilayer acts as an insulator, preventing charged particles (ions) from penetrating it directly. However, specialized proteins called ion transporters and ion channels are embedded within the bilayer, connecting the inside and outside of the cell.

To simplify, let us first assume a hypothetical initial state where the electrolyte composition is identical inside and outside the cell. In reality, ion transporters use energy from ATP to move specific ions against their concentration gradients: $\mathrm{Na}^{+}$, $\mathrm{Ca}^{2+}$, and $\mathrm{Cl}^{-}$ are transported outward, while $\mathrm{K}^{+}$ is transported inward. Additionally, large molecules like protein anions are synthesized and retained within the cell. (In contrast, ion channels allow specific ions to pass through, following their concentration gradients under specific conditions.)

As a result of this active transport and the selective movement through channels, the net electric charge differs between the inside and the outside. This disparity is called the electric potential difference (or membrane potential).

The Na⁺ / K⁺ -ATPase (Sodium-Potassium Transporter) plays the central role in establishing this potential difference. The mechanism is as follows:

Stage (A): In the simplified initial state, assume the concentrations of sodium ions ($\mathrm{Na}^{+}$: pink circles) and potassium ions ($\mathrm{K}^{+}$: red-violet ovals) are equal on both sides. Other major electrolytes, such as $\mathrm{Cl}^{-}$ and $\mathrm{HPO_4^{2-}}$, are distributed according to their standard abundance. The pump initially attracts sodium ions from the inside.


Stage (B): Three $\mathrm{Na}^{+}$ ions are bound within the Sodium-Potassium Transporter.


Stages (C) and (D): Driven by ATP, the transporter changes its conformation, opening to the outside and releasing the three $\mathrm{Na}^{+}$ ions into the extracellular fluid.




Stage (E), the Sodium-Potassium Transporter now attracts extracellular potassium ions ($\mathrm{K}^{+}$).


Stage (F), two $\mathrm{K}^{+}$ ions are bound within the transporter.


Stages (G) and (H), the transporter opens toward the inside, and the two $\mathrm{K}^{+}$ ions are released into the intracellular fluid.




Through this cycle, three $\mathrm{Na}^{+}$ ions are removed from the cell while only two $\mathrm{K}^{+}$ ions are taken in. This net loss of positive charge causes the inside of the cell to become negatively charged relative to the outside.

As a result, the electrolyte concentrations stabilize as previously mentioned: Extracellular fluid (ECF): $\mathrm{Na}^{+}$ 138 mEq/L, $\mathrm{K}^{+}$ 5 mEq/L, $\mathrm{Ca}^{2+}$ 5 mEq/L, $\mathrm{Cl}^{-}$ 113 mEq/L, etc. Intracellular fluid (ICF): $\mathrm{Na}^{+}$ 14 mEq/L, $\mathrm{K}^{+}$ 140 mEq/L, $\mathrm{Ca}^{2+}$ 0.0002 mEq/L, $\mathrm{Cl}^{-}$ 4 mEq/L, etc. This balanced yet polarized state is known as the "resting state." In this state, the electrical potential inside the cell is approximately $-70 \text{ mV}$ (millivolts) relative to the outside. This value is called the "resting potential."

* "Ion Transporter on Wikipedia" https://en.wikipedia.org/wiki/Ion_transporter
* "Na+K+-ATPase on Wikipedia" https://en.wikipedia.org/wiki/NaKATPase






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