Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp ypertension is the most common chronic disease in developed and developing societies and a major risk factor for morbidity and mortality. 1, 2 The most common form of hypertension is 'essential hypertension' the causes of which remain unknown. Among the many factors implicated in the pathophysiology of hypertension are neurohumoral, renal, metabolic, race, genetic, environmental factors and alterations in cellular cations, such as sodium (Na + ), calcium (Ca 2+ ), potassium (K + ) and magnesium (Mg 2+ ) have been shown to be related to the increase in systolic blood pressure. 3-7Mg 2+ , an abundant intracellular divalent cation, functions as an allosteric modulator of several proteins, controls nucleotide and protein synthesis, regulates Na + , K + , and Ca 2+ channels and is critical for myriad enzymatic reactions, particularly those involving kinases. 8,9 Mg 2+ is stored primarily in bone and the intracellular compartments of muscle and soft tissues, with less than 1% of total body Mg 2+ circulating in the blood. 9,10 Mg 2+ homeostasis depends primarily on the balance between intestinal uptake and renal excretion. Mg 2+ deficiency results from reduced dietary intake, intestinal malabsorption or renal loss. Mammalian cells tightly control magnesium levels within a narrow range (0.70-1.1 mmol/L) by specific regulatory mechanisms operating at the level of intraorganelle compartmentalization, intracellular magnesium buffering and at regulating magnesium entry and efflux across the cell membrane.Epidemiological studies indicate that low Mg 2+ status is associated with many diseases including diabetes, metabolic syndrome, dyslipidemia and hypertension.

TRPM7 regulates vascular endothelial cell adhesion and tube formation

“…TRPM7 has been shown to be expressed in the human vascular system and to play a role in vascular functions (3,4,6,25,31,52,68,69,74,76). For example, in vascular smooth muscle cells, TRPM7 modulates Mg 2ϩ homeostasis (6,25).…”

Pulsatile Atheroprone Shear Stress Affects the Expression of Transient Receptor Potential Channels in Human Endothelial Cells

“…6 Moreover, several subtypes of transient receptor potential (TRP) channels, including transient receptor potential cation channel, subfamily C, member 3 (TRPC3) TRPC6, TRPM7, and TRPV1, have been linked to cardiovascular disease, hypertension, and atherosclerosis. [7][8][9][10][11][12][13] TRP channels are activated by a variety of factors, including chemical stimuli and mechanical stimuli, like shear stress. TRP channels are known to be mechanosensitive, although the specific mechanisms still need to be elucidated.…”

Functional properties of ion channels and transporters in tumour vascularization

“…Finally, TRPM7, a Ca 2þ -and Mg 2þ -permeable channel that regulates Mg 2þ homeostasis, is involved in a number of vascular disorders such as hypertension and dysfunction of endothelial and smooth muscle cells [90]. A notable feature of TRPM7 is the presence of a kinase domain at its C-terminus, making TRPM7 unique among ion channels, and allowing its involvement both in cellular Mg 2þ homeostasis and broad signalling [91].…”