Activated N-methyl-D-aspartate receptors (NMDARs) are known to be a major pathway for excessive entry of calcium ions (Ca2+) into central neurons, which can activate degradation processes and thus cause cell death. As a result, it is now recognized that NMDARs play a key role in the development of many diseases associated with central nervous system (CNS) injury. However, it remains a mystery how NMDAR activity is recruited into cellular processes leading to excitotoxicity, and how NMDAR activity can be controlled at the physiological level. The sodium ion (Na+) is the main cation in the extracellular space. Upon entry into the cell, Na+ can act as a critical second intracellular messenger that regulates many cellular functions. Recent data have shown that intracellular Na+ may be an important signaling factor for upregulation of NMDARs. While the influx of Ca2+ during NMDAR activation down-regulates NMDAR activity, the influx of Na+ provides an essential positive feedback mechanism to overcome Ca2+-induced inhibition, thereby potentiating both NMDAR activity and incoming Ca2+ flux. Extensive research has been conducted to clarify the mechanisms underlying Ca2+-mediated signaling. This review focuses on the role of Na+ in regulating Ca2+-mediated NMDAR signaling and toxicity. Figure 1. In the formation of an ionic compound, metals lose electrons and nonmetals gain electrons to reach one byte. Ionic bonds form between ions of opposite charges.
For example, positively charged sodium ions and negatively charged chloride ions combine to form sodium chloride or table salt crystals, creating a crystalline molecule with zero net charge. Certain salts are called in physiology electrolytes (including sodium, potassium and calcium), ions necessary for the conduction of nerve impulses, muscle contractions and fluid balance. Many sports drinks and supplements provide these ions to replace those lost from the body through sweating during exercise. The chemical reduction are positively charged sodium ions and neutral water molecules. At a reversible cathode, reducing sodium ions requires a higher voltage than reducing water molecules, and applying a voltage high enough to reduce sodium ions would reduce a considerable amount of water. This movement of electrons from one element to another is called electron transfer. As shown in Figure 1, sodium (Na) has only one electron in its outer electron shell. It takes less energy for sodium to give this electron than it takes seven more electrons to fill the outer shell. When sodium loses an electron, it now has 11 protons, 11 neutrons and only 10 electrons, so it has a total charge of +1. It is now called a sodium ion. Chlorine (Cl) in its lowest energy state (called ground state) has seven electrons in its outer shell. Again, it is more energy efficient for chlorine to gain one electron than to lose seven.
Therefore, it tends to gain an electron to create an ion with 17 protons, 17 neutrons and 18 electrons, giving it a net negative charge (-1). It is now called chloride ion. In this example, sodium will give up its only electron to empty its shell, and chlorine will accept this electron to fill its shell. Both ions now satisfy the byte rule and have outermost shells. Since the number of electrons is no longer equal to the number of protons, each is now an ion and has a charge of +1 (sodium cation) or -1 (chloride anion). Note that these transactions can usually only occur simultaneously: for a sodium atom to lose an electron, it must be in the presence of a suitable receptor such as a chlorine atom. In this case, the ion has the same outer shell as the original atom, but now this layer has eight electrons. Once again, the byte rule was respected. The resulting anion, Cl−, is called the chloride ion; Note the slight modification of the suffix (-ide instead of -ine) to create the name of this anion. Figure 3.2 “The formation of a chlorine ion” is a graphical representation of this process. We can use electronic configurations to illustrate the process of electron transfer between sodium atoms and chlorine atoms.
Remember the electronic configuration of sodium in Chapter 2 “Elements, Atoms and the Periodic Table”: With two oppositely charged ions, there is an electrostatic attraction between them because opposite charges attract each other. The resulting combination is the compound sodium chloride. Note that there are no more electrons. The number of electrons that the sodium atom (one) loses is equal to the number of electrons that the chlorine atom (one) gains, so the compound is electrically neutral. In macroscopic samples of sodium chloride, there are billions and billions of sodium and chloride ions, although there are always the same number of cations and anions. As shown in Example 1 (in section 3.1 “Two types of bond”), sodium is likely to reach one byte in its outermost shell by losing a valence electron. The remaining species has the following electronic configuration: Figure 3.1 The formation of a sodium ion. On the left, a sodium atom has 11 electrons. On the right, the sodium ion has only 10 electrons and a charge of 1+. The cation thus produced, Na+, is called a sodium ion to distinguish it from the element. The outermost layer of the sodium ion is the second electron shell, in which there are eight electrons.
The byte rule was respected. Figure 3.1 “The formation of a sodium ion” is a graphical representation of this process. Chemists use simple diagrams to show an atom`s valence electrons and their transfer. These diagrams have two advantages over the electron shell diagrams presented in Chapter 2 “Elements, Atoms and the Periodic Table”. First, they only show valence electrons. Second, instead of having a circle around the chemical symbol to represent the electron shell, they have up to eight dots around the symbol; Each point represents a valence electron. These dots are arranged to the right and left and above and below the symbol, with no more than two dots on one side. For example, the representation of sodium is as follows: The loss of sodium ions from circulating plasma in the urine due to the action of endogenous chemicals or drugs on the sodium transport process that occurs in the proximal and distal segments of the renal tubules. Only one more electron is needed to reach one byte in the chlorine valence layer. (In table salt, this electron comes from the sodium atom.) The resulting electronic configuration of the new species is as follows: Most of the elements that form ionic compounds form an ion, which has a characteristic charge. For example, sodium makes ionic compounds in which the sodium ion always has a 1+ charge.
Chlorine forms ionic compounds in which the chloride ion always has a charge of 1−. Some elements, especially transition metals, can form ions with multiple charges. Figure 3.5 “Monatomic ionic charges” shows the characteristic charges of some of these ions. As we saw in Figure 3.1 “The formation of a sodium ion”, there is a model for charges on many ions of the main group, but there is no simple model for transition metal ions (or for the larger elements of the main group). We measured the fluorescence ratio at 346 nm versus 380 nm for the Na+-sensitive dye, sodium-binding benzofuran isophthalate (SBFI) and the Ca2+-sensitive dye, fura-2, in the Soma region of neurons. When the Na+ gradient across the cell membrane was reduced by reducing the extracellular concentration of Na+ ([Na+]e) to 20 mM and the ionophore Na+ monensin (10 μM) was absorbed into the extracellular solution, the basal neurons [Ca2+]i and [Na+]i were approximately 84 nM and 16 mM, respectively. In this condition, bath application of L-aspartate [Ca2+]i increased by 66 nM, decreased [Na+]i by 5.8 mM and inhibited NMDAR 107 activity. On average, the overall channel opening probability and average open time were reduced to 64% and 77% of controls, respectively. Burst and cluster lengths have also been significantly reduced. These inhibitory effects, induced by bath application of L-aspartate, were prevented either by VPA application or by removal of Ca2+ from the extracellular solution, suggesting that activation of distant NMDARs may also downregulate the NMDAR activity recorded by the influx of Ca2+ 107. NMDARs have been shown to be regulated upwards and downwards by Na+ or Ca2+ intakes.
