Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects

Abstract

Wang, Wen-Hui. Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects. Am J Physiol Renal Physiol 290: F14 -F19, 2006; 10.1152/ajprenal. 00093.2005.-This brief review attempts to provide an overview regarding recent developments in the regulation of ROMK channels. Studies performed in ROMK null mice suggest that ROMK cannot only form hometetramers such as the small-conductance (30-pS) K channels but also construct heterotetramers such as the 70-pS K channel in the thick ascending limb (TAL). The expression of ROMK channels in the plasma membrane is regulated by protein tyrosine kinase (PTK), serum and glucorticoid-induced kinase (SGK), and with-no-lysine-kinase 4. PTK is involved in mediating the effect of low K intake on ROMK channel activity. Increases in superoxide anions induced by low dietary K intake are responsible for the stimulation of PTK expression and tyrosine phosphorylation of ROMK channels. Finally, a recent study indicated that ROMK channels can be monoubiquitinated and monoubiquitination regulates the surface expression of ROMK channels.THE ROMK CHANNEL PLAYS AN important role in K recycling in the thick ascending limb (TAL) and K secretion in the connecting tubule (CT) and cortical collecting duct (CCD) (16,19,34,43,45,61). Although maxi-K channels are also possibly involved in the regulation of K secretion in the CCD (66, 67), it is generally agreed that ROMK channels are mainly responsible for K secretion under normal conditions. The regulation of ROMK channels has been extensively studied, and a recent review has provided extensive coverage regarding the regulatory mechanism of ROMK in the past (16). Thus this review is meant to emphasize the newest developments in the field, which may not have been included in previous reviews. Several studies have identified new amino acids that are involved in the regulation of pH sensitivity of ROMK1 channels in addition to lysine residue 80 (14). Also, it has been shown that changes in extracellular K concentrations can affect the sensitivity of ROMK channels to cell pH (9, 49). Although these topics are important to an understanding of the function of ROMK channels, they are beyond the focus of the present review. ROMK IS A KEY COMPONENT OF THE APICAL K CHANNELS IN THE TALApical K channels play an important role in K recycling, which is essential for maintaining the normal function of the Na-K-Cl cotransporter in the TAL (16, 61). Patch-clamp experiments demonstrated that two types of K channels, a 30-to 40-and a 70-to 80-pS, are expressed in the apical membrane of the TAL (3, 59, 62). It is well established that the 30-pS K channel is related to ROMK because it has similar biophysical properties and regulatory mechanisms to that in native tubules (61). However, it is not clear whether ROMK is also involved in forming the apical 70-pS K channel. The observation that the loss-of-function mutations of ROMK result in severe salt wasting and metabolic alkalosis (Bartter's disease) (34, 51) indicates strongly that ROMK is an important component o...

H-K-ATPase type 2: relevance for renal physiology and beyond

“…Here, we only summarize data for rat, human, and mouse species. In Xenopus oocytes, rat HKA2-mediated 86 Rb ϩ flux is insensitive to Sch28080 (administered as a unique dose of 500 M) but is inhibited by ouabain with K i values that depend on extracellular K ϩ concentration (12, 18). These results are in good agreement with the K-ATPase activity present in the rat distal colon that is, indeed, inhibited by ouabain but insensitive to Sch28080 (24, 84).…”

Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function

“…ROMK is predominantly expressed in the kidney where it plays a major role in maintenance of K ϩ homeostasis. Although ROMK activity can be regulated by the CaR (42), it is located in the apical plasma membrane of the thick ascending limb of Henle (TAL) (41,42) while the CaR is in the basolateral membrane (33). We transiently transfected either Myc-Kir4.2 or ROMK into HEK 293 cells that stably express the CaR, and coimmunoprecipitation was performed using our anti-CaR antibody.…”

“…Inhibition of adenylyl cyclase due to CaR stimulation of G␣ i with reduced cAMP accumulation inhibits the activity of NKCC2 and ROMK (22). Phospholipase A 2 activated by the CaR via G␣ q produces arachidonic acid metabolites that inhibit ROMK activity (10,41). The activity of ROMK channels can also be regulated by phosphatidylinositol bisphosphate (PIP 2 ) hydrolysis and synthesis that are regulated by CaR-activated phospholipase C and phosphatidylinositol-4 kinase (16,45).…”

AP-2-dependent Internalization of Potassium Channel Kir2.3 Is Driven by a Novel Di-hydrophobic Signal

“…In recent years, it has become evident that physiological activity of Kir channels is not simply controlled by gating mechanisms (2) but also strongly influenced by surprisingly complex intracellular trafficking processes (3,4). Individually tailored for specific physiological demands, different members of the Kir family are thought to contain unique repertoires of trafficking signals, directing traffic in the biosynthetic pathway as well as between the endosomal compartments and plasma membrane.…”