372 MAGNESIUM SIGNALLING IN CARDIOVASCULAR FUNCTION

Magnesium (Mg2+) is an essential cation critical to many of the biochemical and cellular processes required for cardiovascular function, including DNA replication, protein synthesis and oxidative phosphorylation. Mg2+ levels are tightly regulated in both the whole body and at a cellular level, yet when compared to other cations such as calcium and sodium little is known about the mechanisms regulating Mg2+ signalling and homeostasis. Whilst Mg2+ is known to act as a vasodilator, increasing evidence suggests that Mg2+ signalling may play a broader role in cardiovascular physiology. Low levels of Mg2+ can contribute to the pathogenesis and progression of cardiovascular damage in chronic disease, although the mechanisms underlying this phenomenon remain poorly understood. The transient potential receptor melastatin 7 (TRPM7) channel has been identified as the major mechanism responsible for transporting Mg2+ across the plasma membrane and maintaining cellular Mg2+ homeostasis. This unique protein contains both a Mg2+ and Ca2+-permeable pore and an active kinase domain, and is essential for cell viability and embryonic development. We and others have shown that vascular TRPM7 is upregulated in hypomagnesaemia, type II diabetes and angiotensin II-induced hypertension, and may be contributing to the cardiovascular remodelling and inflammation seen in these diseases. This presentation will discuss some recent work examining the role of TRPM7 in cardiovascular function, with a focus on the potential mechanisms by which alterations in TRPM7/Mg2+-signalling may influence the progression of cardiovascular disease.