CHANNELS, 2021, VOL. 15, NO. 1, 360–374 .https://doi.org/10.1080/19336950.2021.1905248
Wentong Long,Janyne JohnsonORCID Icon,Subha Kalyaanamoorthy &Peter LightORCID Icon
Vitamin D is known to elicit many biological effects in diverse tissue types and is thought to act almost exclusively upon its canonical receptor within the nucleus, leading to gene transcriptional changes and the subsequent cellular response. However, not all the observed effects of vitamin D can be attributed to this sole mechanism, and other cellular targets likely exist but remain to be identified. Our recent discovery that vitamin D is a partial agonist of the Transient Receptor Potential Vanilloid family 1 (TRPV1) channel may provide new insights as to how this important vitamin exerts its biological effects either independently or in addition to the nuclear vitamin D receptor. In this review, we discuss the literature surrounding this apparent discrepancy in vitamin D signaling and compare vitamin D with known TRPV1 ligands with respect to their binding to TRPV1. Furthermore, we provide evidence supporting the notion that this novel vitamin D/TRPV1 axis may explain some of the beneficial actions of this vitamin in disease states where TRPV1 expression and vitamin D deficiency are known to overlap. Finally, we discuss whether vitamin D may also act on other members of the TRP family of ion channels.