Abstract
Magnesium (Mg(2+)) is the second most abundant cellular cation and is essential for all stages of life, from the early embryo to adult. Mg(2+) deficiency causes or contributes to many human diseases, including migraine headaches, Parkinson's disease, Alzheimer's disease, hypotension, type 2 diabetes mellitus and cardiac arrhythmias. Although the concentration of Mg(2+) in the extracellular environment can vary significantly, the total intracellular Mg(2+) concentration is actively maintained within a relatively narrow range (14 - 20 mM) via tight, yet poorly understood, regulation of intracellular Mg(2+)by Mg(2+) transporters and Mg(2+)-permeant ion channels. Recent studies have continued to add to the growing number of Mg(2+) transporters and ion channels involved in Mg(2+) homeostasis, including TRPM6 and TRPM7, members of the transient receptor potential (TRP) ion channel family. Mutations in TRPM6, including amino acid substitutions that prevent its heterooligomerization with TRPM7, occur in the rare autosomal-recessive disease hypomagnesemia with secondary hypocalcemia (HSH). Genetic ablation of either gene in mice results in early embryonic lethality, raising the question of whether these channels' capacity to mediate Mg(2+) influx plays an important role in embryonic development. Here we review what is known of the function of Mg(2+) in early development and summarize recent findings regarding the function of the TRPM6 and TRPM7 ion channels during embryogenesis.