The d subunit of epithelial sodium channel in humans—a potential player in vascular physiology

Abstract

Vascular epithelial sodium channels (ENaCs) made up of canonical a, b, and c subunits have attracted more attention recently owing to their physiological role in vascular health and disease. A fourth subunit, d-ENaC, is expressed in various mammalian species, except mice and rats, which are common animal models for cardiovascular research. Accordingly, d-ENaC is the least understood subunit. However, the recent discovery of d subunit in human vascular cells indicates that this subunit may play a significant role in normal/pathological vascular physiology in humans. Channels containing the d subunit have different biophysical and pharmacological properties compared with channels containing the a subunit, with the potential to alter the vascular function of ENaC in health and disease. Hence, it is important to investigate the expression and function of d-ENaC in the vasculature to identify whether d-ENaC is a potential new drug target for the treatment of cardiovascular disease. In this review, we will focus on the existing knowledge of d-ENaC and implications for vascular physiology and pathophysiology in humans.