Blood vessels are essential for animal life, allowing flow of oxygen and nutrients to tissues and removal of waste products. Consequently, inappropriate remodelling of blood vessels, resulting in occlusion, can lead to disabling or catastrophic events: heart attacks, strokes and claudication. An important cell type of remodelling is the VSMC (vascular smooth-muscle cell), a fascinating cell that contributes significantly to occlusive vascular diseases by virtue of its ability to ‘modulate’ to a cell that no longer contracts and arranges radially in the medial layer of the vessel wall but migrates, invades, proliferates and adopts phenotypes of other cells. An intriguing aspect of modulation is switching to different ion transport systems. Initial events include loss of the CaV1.2 (L-type voltage-gated calcium) channel and gain of the KCa3.1 (IKCa) potassium channel, which putatively occur to enable membrane hyperpolarization that increases rather than decreases a type of calcium entry coupled with cell cycle activity, cell proliferation and cell migration. This type of calcium entry is related to store- and receptor-operated calcium entry phenomena, which, in VSMCs, are contributed to by TRPC [TRP (transient receptor potential) canonical] channel subunits. Instead of being voltage-gated, these channels are chemically gated – importantly, by key phospholipid factors of vascular development and disease. This brief review focuses on the hypothesis that the transition to a modulated cell may require a switch from predominantly voltage- to predominantly lipid-sensing ion channels.

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