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


RESULTS
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.


CONCLUSIONS
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.
Wang
Wen-Hui
WH
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA. wenhui_wang@nymc.edu
Yue
Peng
P
Sun
Peng
P
Lin
Dao-Hong
DH
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005966:Glucuronidase / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D000090265:Klotho Proteins; D008274:Magnesium / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009399:Nephrons / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D000076204:WNK Lysine-Deficient Protein Kinase 1; D019061:src-Family Kinases / Q000502:physiology; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D017868:Cyclic AMP-Dependent Protein Kinases; D005966:Glucuronidase; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000090265:Klotho Proteins; D008274:Magnesium; D015778:Minor Histocompatibility Antigens; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; D019061:src-Family Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C086989:KCNJ1 protein, human; C498743:WNK1 protein, human; C433806:WNK4 protein, human