Pharmacology of transient receptor potential melastatin channels in the vasculature

Abstract

Mammalian transient receptor potential melastatin (TRPM) non-selective cation channels, the largest TRP subfamily, are widely expressed in excitable and non-excitable cells where they perform diverse functions ranging from detection of cold, taste, osmolarity, redox state and pH to control of Mg(2+) homeostasis and cell proliferation or death. Recently, TRPM gene expression has been identified in vascular smooth muscles with dominance of the TRPM8 channel. There has been in parallel considerable progress in decoding the functional roles of several TRPMs in the vasculature. This research on native cells is aided by the knowledge of the activation mechanisms and pharmacological properties of heterologously expressed TRPM subtypes. This paper summarizes the present state of knowledge of vascular TRPM channels and outlines several anticipated directions of future research in this area.

Figures

Figure 1

TRPM subtypes expressed in vascular smooth muscle cells and their established (bold) as well as hypothetical physiological roles in the vasculature. The diagram highlights some structural features of TRPM channels as well as their subtype-specific regulation by membrane potential (V – activation by membrane depolarization), G protein-coupled receptors (GPCR: orange – activation; grey – inhibition; mixed colour – dual effect) and PIP2 (potentiation). CAN, Ca2+-activated non-selective channels; PIP2, phosphatidylinositol-4,5-bisphosphate; SOC, store-operated channel; TRPM, transient receptor potential melastatin.