Aldosterone-independent regulation of K+ secretion in the distal nephron

Abstract

Purpose of review Maintenance of plasma K+ concentration within a narrow range is critical to all cellular functions. The kidneys are the central organ for K+ excretion, and robust renal excretory responses to dietary K+ loads are essential for survival. Recent advances in the field have challenged the view that aldosterone is at the center of K+ regulation. This review will examine recent findings and propose a new mechanism for regulating K+ secretion. Recent findings Local aldosterone-independent response systems in the distal nephron are increasingly recognized as key components of the rapid response to an acute K+ load, as well as playing an essential role in sustained responses to increased dietary K+. The master kinase mTOR, best known for its role in mediating the effects of growth factors and insulin on growth and cellular metabolism, is central to these aldosterone-independent responses. Recent studies have shown that mTOR, particularly in the context of the “type 2” complex (mTORC2), is regulated by K+ in a cell-autonomous fashion. Summary New concepts related to cell-autonomous K+ signaling and how it interfaces with aldosterone-dependent regulation are emerging. The underlying signaling pathways and effectors of regulated K+ secretion, as well as implications for the aldosterone paradox and disease pathogenesis are discussed.