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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Curr+Opin+Nephrol+Hypertens
2016 ; 25
(5
): 429-35
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Basolateral Kir4 1 activity in the distal convoluted tubule regulates K secretion
by determining NaCl cotransporter activity
#MMPMID27306796
Wang WH
Curr Opin Nephrol Hypertens
2016[Sep]; 25
(5
): 429-35
PMID27306796
show ga
PURPOSE OF REVIEW: Renal potassium (K) secretion plays a key role in maintaining
K homeostasis. The classic mechanism of renal K secretion is focused on the
connecting tubule and cortical collecting duct, in which K is uptaken by
basolateral Na-K-ATPase and is secreted into the lumen by apical ROMK (Kir1.1)
and Ca-activated big conductance K channel. Recently, genetic studies and animal
models have indicated that inwardly rectifying K channel 4.1 (Kir4.1 or Kcnj10)
in the distal convoluted tubule (DCT) may play a role in the regulation of K
secretion in the aldosterone-sensitive distal nephron by targeting the NaCl
cotransporter (NCC). This review summarizes recent progresses regarding the role
of Kir4.1 in the regulation of NCC and K secretion. RECENT FINDINGS: Kir4.1 is
expressed in the basolateral membrane of the DCT, and plays a predominant role in
contributing to the basolateral K conductance and in participating in the
generation of negative membrane potential. Kir4.1 is also the substrate of
src-family tyrosine kinase and the stimulation of src-family tyrosine kinase
activates Kir4.1 activity in the DCT. The genetic deletion or functional
inhibition of Kir4.1 depolarizes the membrane of the DCT, inhibits
ste20-proline-alanine rich kinase, and suppresses NCC activity. Moreover, the
downregulation of Kir4.1 increases epithelial Na channel expression in the
collecting duct and urinary K excretion. Finally, mice with low Kir4.1 activity
in the DCT are hypomagnesemia and hypokalemia. SUMMARY: Recent progress in
exploring the regulation and the function of Kir4.1 in the DCT strongly indicates
that Kir4.1plays an important role in initiating the regulation of renal K
secretion by targeting NCC and it may serves as a K sensor in the kidney.