Intracellular Magnesium Metabolism

ß-Adrenergic receptor

Extracellular [Mg2-] = 0.7-1.2mmol

Mg2-

Plasma membrane

Adenylyl cyclase —cAMR

Nucle

Nucle

ATR-Mg

ADR ATR^Mg

Mg2-

Adenylyl cyclase —cAMR

ATR-Mg

ADR ATR^Mg

Mg2-

Rlasma membrane

Muscarinic receptor or vasopressin receptor

Extracellular

FIGURE 4-3

Regulation of intracellular magnesium (Mg2+) in the mammalian cell. Shown is an example of Mg2+ movement between intracellular and extracellular spaces and within intracellular compartments. The stimulation of adenylate cyclase activity (eg, through stimulation of ^-adrenergic receptors) increases cyclic adenosine monophosphate (cAMP). The increase in cAMP induces extrusion of Mg from mitochondria by way of mitochondrial adenine nucleotide translocase, which exchanges 1 Mg2+-adenosine triphosphate (ATP) for adenosine diphosphate (ADP). This slight increase in cytosolic Mg2+ can then be extruded through the plasma membrane by way of a Mg-cation exchange mechanism, which may be activated by either cAMP or Mg. Activation of other cell receptors (eg, muscarinic receptor or vasopressin receptor) may alter cAMP levels or produce diacyl-

glycerol (DAG). DAG activates Mg influx by way of protein kinase C (pK C) activity. Mitochondria may accumulate Mg by the exchange of a cytosolic Mg2+-ATP for a mitochondrial matrix Pi molecule. This exchange mechanism is Ca2+-activated and bidirectional, depending on the concentrations of Mg2+-ATP and Pi in the cytosol and mitochondria. Inositol 1,4,5-trisphos-phate (IP3) may also increase the release of Mg from endoplasmic reticulum or sar-coplasmic reticulum (ER or SR, respectively), which also has a positive effect on this Mg2+-ATP-Pi exchanger. Other potential mechanisms affecting cytosolic Mg include a hypothetical Ca2+-Mg2+ exchanger located in the ER and transport proteins that can allow the accumulation of Mg within the nucleus or ER. A balance must exist between passive entry of Mg into the cell and an active efflux mechanism because the concentration gradient favors the movement of extracellular Mg (0.7-1.2 mmol) into the cell (free Mg, 0.5 mmol). This Mg extrusion process may be energy-requiring or may be coupled to the movement of other cations. The cellular movement of Mg generally is not involved in the transepithelial transport of Mg, which is primarily passive and occurs between cells [1-3,7]. (From Romani and coworkers [3]; with permission.)

Mg2+ Mitochondrion

Extracellular

Mg2+

Outer membrane

Extracellular

Mg2+

Outer membrane

2+ Periplasm

ATP MgtA

Mg Cytosol

Mg2+

2+ Periplasm

ATP MgtA

Mg Cytosol

Mg2+

FIGURE 4-4

A, Transport systems of magnesium (Mg). Specific membrane-associated Mg transport proteins only have been described in bacteria such as Salmonella. Although similar transport proteins are believed to be present in mammalian cells based on nucleotide sequence analysis, they have not yet been demonstrated. Both MgtA and MgtB (molecular weight, 91 and 101 kDa, respectively) are members of the adenosine triphosphatase (ATPase) family of transport proteins. B, Both of these transport proteins have six C-terminal and four N-terminal membrane-spanning segments, with both the N- and C-terminals within the cytoplasm. Both proteins transport Mg with its electrochemical gradient, in contrast to other known ATPase proteins that usually transport ions

Periplasm

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