The surge of flavonoids as novel, fine regulators of cardiovascular Cav channels

Abstract

Ion channels underlie a wide variety of physiological processes that involve rapid changes in cell dynamics, such as cardiac and vascular smooth muscle contraction. Overexpression or dysfunction of these membrane proteins are the basis of many cardiovascular diseases that represent the leading cause of morbidity and mortality for human beings. In the last few years, flavonoids, widely distributed in the plant kingdom, have attracted the interest of many laboratories as an emerging class of fine ion, in particular Ca_v, channels modulators. Pieces of in vitro evidence for direct as well as indirect effects exerted by various flavonoids on ion channel currents are now accumulating in the scientific literature. This activity may be responsible, at least in part, for the beneficial and protective effects of dietary flavonoids toward cardiovascular diseases highlighted in several epidemiological studies. Here we examine numerous studies aimed at analysing this feature of flavonoids, focusing on the mechanisms that promote their sometimes controversial activities at cardiovascular Ca_v channels. New methodological approaches, such as molecular modelling and docking to Ca_v1.2 channel α_1c subunit, used to elucidate flavonoids intrinsic mechanism of action, are introduced. Moreover, flavonoid-membrane interaction, bioavailability, and antioxidant activity are taken into account and discussed.

Keywords: (S)-(-)-Bay K 8644 (PubChem CID: 6603728); Ca(v)1.2 channel; Cardiovascular system; Daidzein (PubChem CID: 5281708); Flavonoid; Genistein (PubChem CID: 5280961); Molecular docking; Myricetin (PubChem CID: 5281672); Patch-clamp; Quercetin; Quercetin (PubChem CID: 5280343).