MEMBRANE PROCESSES MEDIATING K+ SECRETION

Weill Medical College Of Cornell Univ, New York NY

Investigators

Linked publications & trials

Abstract

DESCRIPTION (Adapted from the Applicant's Abstract): The kidney maintains the appropriate amounts of potassium in the body by matching the amounts of salt excreted to those which are in the diet. The final regulation of K+ balance is thought to occur in the collecting tubule. Here, the amount of K+ secreted or absorbed depends on the activities of apical K+ channels. Previous work showed that when dietary K+ is high, the density of apical K+ channels is increased through a mechanism which is independent of aldosterone. In the proposed research they will explore this regulatory process further, focusing on the systems controlling the K+ channels. Experimental studies will involve the use of a combination of electrophysiological and molecular biological approaches. They will explore in detail the relationship between K+ channel density and dietaryes, they will examine the time course and load dependence of the upregulation of conducting K+ channel density. They will also test whether the channels are downregulated in animals on a K+-restricted diet. The principal investigator will test the hypothesis that increased levels of mRNA underly the control of the density of conducting channels using quantitative in situ hybridization techniques. The principal investigator will use antibodies raised against the K+ channel to map the sites of apical K+ channel expression and to assess the role of changes in the amount of K+ channel protein in the regulatory process. He will also explore the relationship between the long-term regulation of the K+ channels with more short-term processes. These will include both regulation through cAMP and PKA, and channel activation by acute elevation of extracellular K+. The biophysical and molecular basis for the latter effect will also be studied using the Xenopus oocyte expression system. This research should help illuminate how K+ transport by the distal nephron is regulated during health (changes in diet) and disease (e.g. renal insufficiency). It will also help to clarify how Na+ and K+ transport can be regulated separately in the collecting tubule to maintain blood volume and pressure as well as plasma K+ concentration within narrow limits.