TRPM Channels in the Vasculature
Alexander Zholos, Christopher Johnson, Theodor Burdyga, and Donal Melanaphy
Recent studies show that mammalian melastatin TRPM nonselective cation channels (TRPM1-8), members of the largest and most diverse TRP subfamily, are widely expressed in the endothelium and vascular smooth muscles. When activated, these channels similarly to other TRPs permit the entry of sodium, calcium and magnesium, thus causing membrane depolarisation. Although membrane depolarisation reduces the driving force for calcium entry via TRPMs as well as other pathways for calcium entry, in smooth muscle myocytes expressing voltage-gated Ca2+ channels the predominant functional effect is an increase in intracellular Ca2+ concentration and myocyte contraction. This review focuses on several best documented aspects of vascular functions of TRPMs, including the role of TRPM2 in oxidant stress, regulation of endothelial permeability and cell death, the connection between TRPM4 and myogenic response, significance of TRPM7 for magnesium homeostasis, vessel injury and hypertension, and emerging evidence that the cold and menthol receptor TRPM8 is involved in the regulation of vascular tone.