Regulation and function of potassium channels in aldosterone-sensitive distal nephron

Curr Opin Nephrol Hypertens. 2010 Sep;19(5):463-70. doi: 10.1097/MNH.0b013e32833c34ec.

Abstract

Purpose of review: K channels in the aldosterone-sensitive distal nephron (ASDN) participate in generating cell membrane potential and in mediating K secretion. The aim of the review is to provide an overview of the recent development regarding physiological function of the K channels and the novel factors which modulate the K channels of the ASDN.

Recent findings: Genetic studies and transgenic mouse models have revealed the physiological function of basolateral K channels including inwardly rectifying K channel (Kir) and Ca-activated big-conductance K channels in mediating salt transport in the ASDN. A recent study shows that intersectin is required for mediating with-no-lysine kinase (WNK)-induced endocytosis. Moreover, a clathrin adaptor, autosomal recessive hypercholesterolemia (ARH), and an aging-suppression protein, Klothe, have been shown to regulate the endocytosis of renal outer medullary potassium (ROMK) channel. Also, serum-glucocorticoids-induced kinase I (SGK1) reversed the inhibitory effect of WNK4 on ROMK through the phosphorylation of WNK4. However, Src-family protein tyrosine kinase (SFK) abolished the effect of SGK1 on WNK4 and restored the WNK4-induced inhibition of ROMK.

Summary: Basolateral K channels including big-conductance K channel and Kir4.1/5.1 play an important role in regulating Na and Mg transport in the ASDN. Apical K channels are not only responsible for mediating K excretion but they are also involved in regulating transepithelial Mg absorption. New factors and mechanisms by which hormones and dietary K intake regulate apical K secretory channels expand the current knowledge regarding renal K handling.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aldosterone / pharmacology*
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Glucuronidase / physiology
  • Humans
  • Immediate-Early Proteins / physiology
  • Intracellular Signaling Peptides and Proteins
  • Klotho Proteins
  • Magnesium / metabolism
  • Minor Histocompatibility Antigens
  • Nephrons / metabolism*
  • Potassium Channels / physiology*
  • Potassium Channels, Inwardly Rectifying / physiology
  • Potassium Channels, Voltage-Gated / physiology
  • Protein Kinase C / physiology
  • Protein Serine-Threonine Kinases / physiology
  • WNK Lysine-Deficient Protein Kinase 1
  • src-Family Kinases / physiology

Substances

  • Immediate-Early Proteins
  • Intracellular Signaling Peptides and Proteins
  • KCNJ1 protein, human
  • Minor Histocompatibility Antigens
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Potassium Channels, Voltage-Gated
  • Aldosterone
  • src-Family Kinases
  • Protein Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • WNK1 protein, human
  • WNK4 protein, human
  • serum-glucocorticoid regulated kinase
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Glucuronidase
  • Klotho Proteins
  • Magnesium