Expression and insights on function of potassium channel TWIK-1 in mouse kidney

Abstract

Renal distribution and function of TWIK-1, a member of the two-pore-domain potassium channel family, was studied in mouse kidney. TWIK-1 is expressed in apical and subapical localizations of proximal tubule and cytoplasmic sites of thin and thick ascending limbs, distal convoluted tubules and medullary collecting duct. Studies in mice lacking intact TWIK-1 (twik-1 -/-) and wild-type mice (twik-1 +/+) revealed an attenuated ability to increase renal phosphate (Pi) reabsorption and stabilize plasma Pi concentration in response to a low Pi diet in twik-1 -/- mice. Western blot analysis and immunohistochemistry for the electrogenic 3Na(+)-1HPO(4) (2-)-cotransporter NaPi-2a revealed a reduced reno-cortical expression in twik-1 -/- mice under these conditions. Under normal diet, twik-1 -/- mice presented lower urinary flow rates. Acute pharmacologic blockade of the vasopressin V(2)-receptor revealed both an attenuated diuretic response and an attenuated internalization of aquaporin-2 in the inner medullary collecting duct in twik-1 -/- versus +/+ mice. In summary, mice deficient for TWIK-1 presented impaired regulation of (i) Pi transport in proximal tubule and (ii) water transport in medullary collecting duct. TWIK-1 may contribute to membrane trafficking/expression of transport molecules in proximal tubule and medullary collecting duct, and possibly other renal sites of expression.

Kir4.1/Kir5.1 channel forms the major K+channel in the basolateral membrane of mouse renal collecting duct principal cells

“…First, the TASK-1 channel is only 14 pS (2). Second, TWIK-1, a 34-pS, weakly inward rectifying and ATPinsensitive K ϩ channel, appears only intracellularly located in mouse CCD cells (24), with no detectable activity in cell membranes (20). In addition, TWIK-1 is insensitive to pH i in cell-excised inside-out membrane patches of Xenopus oocytes (14).…”

Renal Phosphate Wasting in the Absence of Adenylyl Cyclase 6

“…12,13 Immunohistochemistry identified Npt2a to be localized predominantly in the apical plasma membrane of S1-S3 segments of the proximal tubule. 6,14,15 Npt2c has a similar cellular distribution with greater abundance in S1 segments. 5,16,17 Genetic defects in G sa result in impaired PTH-induced retrieval of Npt2a, resulting in a failure to respond with increased urinary P i excretion: a disease commonly referred to as pseudohypoparathyroidism type Ia or Ib (depending on the presence or absence of skeletal defects, respectively).…”

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

“…However, in endogenous systems, expression of TWIK-1 has been documented in various tissues, including the brain, heart and kidney 3 . Mice deficient in TWIK-1 show defects in phosphate transport in the proximal tubule and water transport in the medullary collecting duct of kidney, as well as deviations in the resting membrane potential of pancreatic b cells 4,5 . In addition, it has been recently reported that TWIK-1 conducts inward leak Na þ currents during pathological hypokalaemia in cardiomyocytes 6 .…”