Aging, calcium channel signaling and vascular tone

Calcium signaling in vascular smooth muscle is crucial for arterial tone regulation and vascular function. Several proteins, including Ca²⁺ channels, function in an orchestrated fashion so that blood vessels can sense and respond to physiological stimuli such as changes in intravascular pressure. Activation of the voltage-dependent Ca²⁺ channel, Cav1.2, leads to Ca²⁺ influx and consequently arterial tone development and vasoconstriction. Unique among Ca²⁺ channels, the vascular Cav3.2 T-type channel mediates feedback inhibition of arterial tone-and therefore causes vasodilation-of resistance arteries by virtue of functional association with hyperpolarizing ion channels. During aging, several signaling modalities are altered along with vascular remodeling. There is a growing appreciation of how calcium channel signaling alters with aging and how this may affect vascular function. Here, we discuss key determinants of arterial tone development and the crucial involvement of Ca²⁺ channels. We next provide an updated view of key changes in Ca²⁺ channel expression and function during aging and how these affect vascular function. Further, this article synthesizes new questions in light of recent developments. We hope that these questions will outline a roadmap for new research, which, undoubtedly, will unravel a more comprehensive picture of arterial tone dysfunction during aging.