Magnesium Homeostasis in Mammalian Cells

Abstract

Magnesium, the second most abundant cation within the cell, plays an important role in numerous biological functions. Experimental evidence indicates that mammalian cells tightly regulate cellular magnesium ion content through specific mechanisms controlling Mg(2+) entry and efflux across the cell membrane and the membrane of various cellular organelles as well as intracellular Mg(2+) buffering under resting conditions and following hormonal and metabolic stimuli. This chapter will provide an assessment of the various mechanisms controlling cellular Mg(2+) homeostasis and transport, and the implications changes in cellular Mg(2+) content play under physiological and pathological conditions.

Divalent cation signaling in immune cells

“…On the other hand, there is a much smaller difference (< 2-fold) between cytosolic free Mg 2+ ([Mg 2+ ] i ) and extracellular free Mg 2+ ([Mg 2+ ] o ) level leading to the conventional wisdom that it is a poor candidate for a second messenger (Table 1) [1, 2]. However, because non-excitable cells, such as immune cells, harbor a negative membrane potential ≈ −70mV, if intracellular free Mg 2+ was at electrical equilibrium, its resting concentration should be 50 mM [3, 4]. Nevertheless, [Mg 2+ ] i ranges from 0.2 to 0.5 mM, showing that intracellular free Mg 2+ is regulated and maintained at a lower concentration.…”

“…Nevertheless, [Mg 2+ ] i ranges from 0.2 to 0.5 mM, showing that intracellular free Mg 2+ is regulated and maintained at a lower concentration. This creates an electrochemical gradient of 100 to 250-fold for Mg 2+ , which is sufficient to allow rapid mobilization across the plasma membrane (PM) (Table 1, see Regulation of cytosolic free Mg 2+ section) [3, 5, 6]. Indeed, the physiological function of rapid Mg 2+ fluxes in T lymphocytes has been recently demonstrated and led to interesting insights into novel immunoregulatory mechanisms [7].…”

“…It involves Mg 2+ transporters, channels and exchangers, such as the Mg 2+ /Na + exchanger (Figure 1b, Table 2). Another major participant is the melastatin transient receptor potential 7 (TRPM7) channel [3]. TRPM7 is a ubiquitously expressed, non-selective Mg 2+ channel that also conducts Ca 2+ , Zn 2+ and even Na + in absence of divalent cations [3, 20, 21].…”

“…Another major participant is the melastatin transient receptor potential 7 (TRPM7) channel [3]. TRPM7 is a ubiquitously expressed, non-selective Mg 2+ channel that also conducts Ca 2+ , Zn 2+ and even Na + in absence of divalent cations [3, 20, 21]. TRPM7 has a serine/threonine kinase domain in its cytosolic tail [22].…”

“…Whether TRPM7 deficiency affects total, mainly bound, Mg 2+ in B cell lines was not determined [22]. Both TRPM7 and MAGT1 appear to play a role in T cell differentiation [3, 7]. Germline TRPM7 KO mice are embryonic lethal, whereas T cell-specific TRPM7 KO mice are viable but exhibit a blockade of thymic T cell development at the double negative stage [24].…”