We reported previously that inhibition of Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) by bumetanide abolishes high extracellular K(+) concentration ([K(+)](o))-induced swelling and intracellular Cl(-) accumulation in rat cortical astrocytes. In this report, we extended our study by using cortical astrocytes from NKCC1-deficient (NKCC1(-/-)) mice. NKCC1 protein and activity were absent in N...

Mice deficient in Na-K-2Cl cotransporter (NKCC1) have been generated by targeted disruption of the gene encoding NKCC1 involving the carboxy terminus (CT-NKCC1) but not the amino terminus. We hypothesize that the resulting physiological defects are due to loss of proteins interacting with CT-NKCC1. Using a yeast two-hybrid approach, adaptor protein COMMD1 was found to bind to CT-NKCC1 (aa 1,040...

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na+-K+-2Cl- co-transporter 1 (NKCC1) is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. ...

Airways of Na(+)-K(+)-2Cl(-) (NKCC1)-deficient mice (-/-) were studied in Ussing chambers to determine the role of the basolateral NKCC1 in transepithelial anion secretion. The basal short-circuit current (I(sc)) of tracheae and bronchi from adult mice did not differ between NKCC1-/- and normal mice, whereas NKCC1-/- tracheae from neonatal mice exhibited a significantly reduced basal I(sc). In ...

Na–K–Cl cotransporter isoform 1 (NKCC1) plays an important role in maintenance of intracellular Na , K , and Cl levels in astrocytes. We propose that NKCC1 may contribute to perturbations of ionic homeostasis in astrocytes under ischemic conditions. After 3– 8 hr of oxygen and glucose deprivation (OGD), NKCC1-mediated Rb influx was significantly increased in astrocytes from NKCC1 wild-type (NKC...

The Na(+)K(+)2Cl(-) cotransporter-1 (Slc12a2, NKCC1) is widely distributed and involved in cell volume/ion regulation. Functional NKCC1 locates in the plasma membrane of all cells studied, particularly in the basolateral membrane of most polarized cells. Although the mechanisms involved in plasma membrane sorting of NKCC1 are poorly understood, it is assumed that N-glycosylation is necessary. H...

The Na-K-2Cl cotransporter isoform1 (NKCC1) is present in many animal cells where it plays prominent roles in regulating cell volume and maintaining intracellular Cl(-) concentration ([Cl(-)]i) above electrochemical equilibrium. We show here that NKCC1 is present and active in cultured oligodendrocytes. Expression of NKCC1 in the rat spinal cord increased during development from postnatal day 6...

The basolateral Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) functions in the maintenance of cellular electrolyte and volume homeostasis. NKCC1-deficient (Nkcc1(-/-)) mice were used to examine its role in cardiac function and in the maintenance of blood pressure and vascular tone. Tail-cuff measurements demonstrated that awake Nkcc1(-/-) mice had significantly lower systolic blood pressure than wild...

Acute administration of loop diuretics like furosemide leads to a stimulation of renin secretion, an effect thought to result from inhibition of Na-K-2Cl cotransporter (NKCC2)-mediated salt transport at the luminal surface of the macula densa (MD). However, loop diuretics also inhibit NKCC1, the second isoform of the Na-K-2Cl cotransporter, with similar potency. In the present study, we examine...

The Na-K-2Cl cotransporter (NKCC1) is one of several transporters that have been linked to hypertension, and its inhibition reduces vascular smooth muscle tone and blood pressure. NKCC1 in the rat aorta is stimulated by vasoconstrictors and inhibited by nitrovasodilators, and this is linked to the contractile state of the smooth muscle. To determine whether blood pressure also regulates NKCC1, ...