Abstract
Magnesium (Mg2+) is an abundant intra- as well as extracellular divalent cation. It is essential for multiple intracellular processes. Its major reservoir is in the bone. Mg2+ homeostasis is regulated by its absorption from the gut and its secretion or reabsorption by the kidneys through specific transcellular and paracellular Mg2+ channels. Derangements in Mg2+ homeostasis may cause elevations (hypermagnesemia) or decrease (hypomagnesemia) in its blood levels, both potentially causing adverse effects, some of them directly ascribed to Mg2+ effects on the nervous as well as the cardiac electrical conduction systems. Most clinical conditions are associated with hypomagnesemia, whereas most cases of hypermagnesemia are asymptomatic. Subclinical hypomagnesemia may cause cardiovascular disease in adults. Other clinical adverse effects derive from the secondary hypocalcemia in cases of severe hypomagnesemia. Different clinical conditions may cause hypomagnesemia, including acquired (such as chronic diarrhea or medications) and genetic. Most affected genes that cause hypomagnesemia are expressed in the nephron’s distal tubule, mainly the thick ascending limb (such as the paracellin/claudin 16 and claudin 19 genes) and distal convoluted tubule segments (such as the thiazide sensitive channel, TRPM6 and the Na–K-ATPase). Mutations in TRPM6, a channel expressed in both the distal tubule as well as in the small intestine cause early (usually in the first months of life) and severe hypomagnesemia with secondary hypocalcemia. Differentiation between the mutated different genes can be initially approached by several clinical as well as laboratory observations (for example: the presence of hypercalciuria, metabolic alkalosis, etc.). The aim of this chapter is to summarize Mg2+ physiology, its handling by kidney and intestine and the clinical syndromes of Mg2+ derangement, concentrating on a crucial protein involved in Mg2+ reabsorption in both kidney and intestine: TRPM6 channel.
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Landau, D., Shalev, H. (2014). TRPM6 and Hypomagnesaemia/Hypocalcaemia . In: Weiss, N., Koschak, A. (eds) Pathologies of Calcium Channels. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40282-1_25
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DOI: https://doi.org/10.1007/978-3-642-40282-1_25
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