Emerging functions of 10 types of TRP cationic channel in vascular smooth muscle

Abstract

1. The influx of Ca2+, Mg2+ and Na+ and the efflux of K+ have central importance for the function and survival of vascular smooth muscle cells, but progress in understanding the influx/efflux pathways has been restricted by a lack of identification of the genes underlying many of the non-voltage-gated cationic channels. 2. The present review highlights evidence suggesting the genes are mammalian homologues of the Transient Receptor Potential (TRP) gene of the fruit-fly Drosophila. The weight of evidence supports roles for TRPC1, TRPP2/1 and TRPC6, but recent studies point also to TRPC3, TRPC4/5, TRPV2, TRPM4 and TRPM7. 3. Activity of these TRP channels is suggested to modulate contraction and sense changes in intracellular Ca2+ storage, G-protein-coupled receptor activation and osmotic stress. Roles in relation to myogenic tone, actions of vasoconstrictors substances, Mg2+ homeostasis and the vascular injury response are suggested. 4. Knowledge that TRP channels are relevant to vascular smooth muscle cells in both their contractile and proliferative phenotypes should pave the way for a better understanding of vascular biology and provide the basis for the discovery of a new set of therapeutic agents targeted to vascular disease.

Figure 1. Emerging functions of 10 types of TRP cationic channel in vascular smooth muscle

The TRP channels are shown pictorially arranged in a circle in recognition of their membership of one protein family. The circle does not necessarily indicate a physical association with an adjacent TRP. Nevertheless, there is experimental evidence for physical associations between TRPC1 and TRPP2, TRPC1, TRPC3, TRPC4 and TRPC5, and TRPC3 and TRPC6 (see text for references).