How does Magnesium work in muscles and nerves

This is a short introduction of the importance of Magnesium in human bodies.

Only 3 sections to read. If you need further informations, please feel ease to contact us from here.

Since Magnesium is water soluble and the human kidney has the high tendency to wash out Magnesium from human body via urine(i.m.o., the sympathetic nerve stimulant causing Magnesium loss from urine is a major cause of Magnesium depletion in our modern society, the blog entry here), it is recommended that human beings with wholesome kidneys frequently supplement Magnesium in some form, which has been my recommendation since no later than 2021/12/10. It is the story-tellling explanation why human kidney is so Magnesium-resilient is they are still relying on "fish kidney" which allows them to filtrate sea water at all time. 

Biological Function of Ca²⁺ and Mg²⁺

Ca²⁺ influx is the functional trigger of muscle and nerve cells(According to, e.g. Medical Biochemistry By Baynes & Dominiczak - (4rd, Fourth Edition) Japanese translation edition(2018).). Magnesium, a major cation component of the intracellular fluid(ICF) for human body cells, contribute to expel the Ca²⁺ from the cells after the functional event. Cations' in-out flow go through exchangers or channels, e.g. NCX or TRPM family(Calcium clearance mechanism explained here ―unfortunately, this paper neglects TRPM family and other possibly exist channels(my commentary here). Kind reminder: Intracellular Mg²⁺ contributes to the voltage (the difference between inta- and extra-cellular electrochemical potentials) conformation since it is a major component of ICF. Note: On Nerve cells, it is known that Mg²⁺ has the unique role not only on voltage conformation. Details here). If not sufficient Mg²⁺  inside the cell, there may be some trouble by obstacles bringing Ca²⁺ back to the original state(outside the cells), e.g. the muscle stiffness or over-excitation(frequency and duration) of nerves. See this(Google Gemini explanation, on history this) for the further understanding of Calsium-concentration-dependent muscle contraction.

Table 1. Biological function of Ca²⁺ influx and expulsion.

	Ca2+ influx to cell (流入)	Ca2+ expulsion from cell (排出)
Muscle (筋肉)	to contract (収縮)	to relax (弛緩)
Nerve (神経)	to excite (興奮)	to calm down (鎮静)

Fig 1. Google Gemini generated schema for cellular cation in-out. Mg²⁺ contributes to expel Ca²⁺ in order to get back to the original state. 

Magnesium dynamical flow in human body

The serum(in-blood) Mg²⁺ concentration is strictly controlled within the narrow width due to the kidney function. When it comes to the Mg²⁺ shortage in blood flow, it is recruited from the in-body storages like bones or ICF of body cells. Considering the mechanisms described above it means that the Mg²⁺ shortage in blood flow causes it squeezing out Magnesium from ICF or melting bone. 

Fig 2. Copied from this article without permissions of authors. Please contact us if it concerns you. 

Fig 3.  Orally intaked(sometimes injected via vein) mineral ions stay within the body if not discharged via sweat/urine etc. This is Lavoisier's "the law of conservation of mass". The distribution of channels and pumps determines mineral locality.

The function as co-enzyme for over 300 enzymes

Magnesium is known that it functions as co-enzyme for over 300 enzymes including ATP which is the "Energy currency". Many cell functions including muscle contraction and Ca²⁺ expulsion(by PMCA, Google Gemini explanation here) depends on ATP consumption.

Further reading for Magnesium importance is e.g. this.

Appex. Intra- and Extra- cellular Components

Recall: Magnesium is a major cation component of ICF. 

Electrolyte Composition of Body Fluids (mEq/L)

Category	Ion	Plasma (ECF)	Interstitial Fluid (ECF)	Intracellular Fluid (ICF)
Cations (陽イオン)		142	144	15
		4	4	150
		5	2.5	2*
		3	1.5	27*
	Total	154	152	194
Anions (陰イオン)		103	114	1
		27	30	10
		2	2	100
		1	1	20
	Organic Acids	5	5	-
	Proteins	16	0	63
	Total	154	152	194

Barriers between compartments (表の下の境界線)

• Between Plasma and Interstitial Fluid: Capillary Wall (毛細血管壁)

• Between Interstitial Fluid and Intracellular Fluid: Cell Membrane (細胞膜)

Key Characteristics (右側のボックス)

• Abundant in Extracellular Fluid (ECF): Na+, Cl−

• Abundant in Intracellular Fluid (ICF): K+, Mg2+, HPO42−​

Footnotes & References (注釈・出典)

Note (*): In the Intracellular Fluid (ICF), the values represent total concentrations, including those bound to proteins. The concentrations of free ions for Ca2+ and Mg2+ are 2×10−4 mEq/L and 1 mEq/L, respectively.

Sources: > 1. Shozo Koshikawa, Fluid Therapy, Chugai-Igakusha, 1985, p.17. 2. Yoshihiro Kubo (Ed.), Standard Physiology 8th Ed., Igaku-Shoin, 2014, p.53. English translation by Google Gemini here.