Atlas One · Atomic · Alkaline Earth / Enzyme Cofactor / Electrolyte
Period 3, Group 2 — second most abundant intracellular cation (after K⁺)
| Property | Value |
|---|---|
| Atomic mass | 24.31 Da |
| Ionic radius | 0.72 Å (smaller than Ca²⁺ 1.00 Å — higher charge density) |
| Intracellular free [Mg²⁺] | 0.5–1.0 mmol/L free; 5–20 mmol/L total (mostly Mg-ATP) |
| Bone content | ~60% of body Mg; surface-exchangeable pool important for buffering |
| Muscle content | ~25%; primarily as Mg-ATP and Mg-ADP |
| Dietary sources | Nuts, seeds, legumes, whole grains, green leafy vegetables, dark chocolate |
| Absorption site | Ileum/colon (~30–40% of dietary Mg); TRPM6/7 channels |
Biological Roles
Mg-ATP²⁻ as universal kinase substrate; NMDA receptor voltage-dependent block; cardiac Ca²⁺ antagonism
Mg²⁺ in ATP Biochemistry and Signalling
All ATP-dependent reactions require Mg²⁺ as Mg-ATP²⁻ chelate:
Mg²⁺ + ATP⁴⁻ ⇌ Mg-ATP²⁻ (Kd ~0.1 mmol/L)
↓
Kinases (≥300 reactions):
Hexokinase, PFK-1, Pyruvate kinase
Protein kinases (PKA, PKC, CaMKII, AMPK)
ATPases: Na⁺/K⁺-ATPase, SERCA, myosin-ATPase
DNA polymerase / RNA polymerase
↓
Structural role in DNA/RNA — stabilises
phosphodiester backbone negative charges
NMDA Receptor — Mg²⁺ Voltage-Dependent Pore Block:
Resting membrane (~−70 mV):
Mg²⁺ occupies channel pore → NMDA receptor blocked
(both glutamate and glycine bound but no current)
↓
Depolarisation (AMPA-mediated ~−30 mV):
Mg²⁺ expelled from pore by positive Vm
NMDA opens → Ca²⁺ influx → LTP induction (coincidence detector)
Cardiovascular Roles
Mg²⁺ competes with Ca²⁺ at L-type (Cav1.2) and T-type Ca²⁺ channels in vascular smooth muscle (VSM), causing vasodilation. In cardiac muscle, Mg²⁺ reduces automaticity of ectopic pacemakers. Intravenous MgSO₄ is first-line treatment for torsades de pointes (TdP) by stabilising the cardiac resting potential and suppressing early afterdepolarisations (EADs).
Mg²⁺ and Pre-eclampsia
MgSO₄ (4 g IV loading dose; 1–2 g/h maintenance) prevents and treats eclamptic seizures, likely by blocking NMDA receptors in cerebral vasculature, reducing cerebral vasospasm and preventing cortical spreading depression. Mg level monitoring (deep tendon reflex loss at ~4–5 mmol/L; respiratory paralysis at >6 mmol/L) is essential.
Absorption & Metabolism
TRPM6/7 epithelial transport; claudin-16/19 paracellular reabsorption in TAL
| Transporter/Channel | Location | Function |
|---|---|---|
| TRPM7 | All tissues (ubiquitous) | Constitutive Mg²⁺ entry; also Zn²⁺, Ca²⁺; channel-kinase fusion protein |
| TRPM6 | Intestinal epithelium (apical), distal tubule | Dietary Mg²⁺ absorption; regulated by EGF and oestrogen |
| Claudin-16 / claudin-19 | Thick ascending limb (TAL) | Paracellular cation selectivity filter — Mg²⁺ and Ca²⁺ reabsorption driven by lumen-positive voltage (NaKCl2 + ROMK) |
| CNNM2 / SLC41A1 | Distal tubule basolateral | Mg²⁺ efflux into blood; loss-of-function → hypomagnesaemia |
~70% of plasma Mg²⁺ is filtered; ~95% reabsorbed (60% TAL paracellular, 10% DCT transcellular via TRPM6). Aldosterone and thiazide diuretics → ↓ DCT Mg²⁺ reabsorption. PTH and calcitriol promote TRPM6 expression.
Deficiency & Toxicity
| Status | Serum Mg²⁺ | Signs | Treatment |
|---|---|---|---|
| Severe hypomagnesaemia | <0.4 mmol/L | Tetany, seizures, torsades de pointes (TdP), hypokalaemia (K⁺ renal wasting), hypocalcaemia (↓ PTH secretion/action) | IV MgSO₄ (1–2 g over 5–10 min for TdP); oral Mg supplementation |
| Mild hypomagnesaemia | 0.4–0.74 mmol/L | Muscle cramps, tremor, fatigue, anxiety, hypertension, insulin resistance | Oral magnesium oxide/citrate/glycinate; dietary improvement |
| Normal | 0.75–1.0 mmol/L | — | — |
| Hypermagnesaemia (usually iatrogenic) | >2 mmol/L | Loss of deep tendon reflexes, somnolence, hypotension, bradycardia | IV calcium gluconate (antagonises Mg²⁺); haemodialysis in severe cases |
| Lethal hypermagnesaemia | >6 mmol/L | Respiratory paralysis, cardiac arrest | Emergency calcium; ventilatory support; haemodialysis |
Hypomagnesaemia causes refractory hypokalaemia (Mg²⁺ required for ROMK-mediated K⁺ reabsorption in distal nephron) and hypocalcaemia (Mg²⁺ required for PTH secretion and PTH receptor signalling). Correct Mg²⁺ first when managing these electrolyte disturbances.
Clinical Use
| Application | Details |
|---|---|
| Torsades de pointes | IV MgSO₄ 2 g over 1–2 min; suppresses EADs regardless of serum Mg²⁺ level |
| Pre-eclampsia/eclampsia | MgSO₄ Pritchard/Sibai regimen; reduces seizure recurrence (vs. diazepam, Magpie trial) |
| Asthma (refractory) | IV MgSO₄ 2 g over 20 min; bronchodilation via smooth muscle Ca²⁺ channel antagonism |
| Pre-term labour tocolysis | MgSO₄ short-term neuroprotection for <32-week fetuses (reduces CP risk, ACT trial) |
| Laxative / bowel prep | Oral magnesium citrate / Mg(OH)₂ — osmotic laxative effect |
Connections
References
- de Baaij JHF, Hoenderop JGJ, Bindels RJM. "Magnesium in man: implications for health and disease." Physiol Rev 2015;95:1–46.
- Magpie Trial Collaborative Group. "Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate?" Lancet 2002;359:1877–1890.
- DiNicolantonio JJ, O'Keefe JH, Wilson W. "Subclinical magnesium deficiency: a principal driver of cardiovascular disease." Open Heart 2018;5:e000668.
- Schlingmann KP, et al. "Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6." Nat Genet 2002;31:166–170.