Disease relevance of Clcnkb

• Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent [1].

High impact information on Clcnkb

• These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents [1].
• These results suggest that ClC-K2L and -K2S are chloride channels in the thick ascending limb and collecting ducts and may be important routes for transcellular chloride transport like ClC-K1 [2].
• Complementary DNAs encoding rat kidney chloride channels (ClC-K2L and ClC-K2S) were isolated by a polymerase chain reaction cloning strategy [2].
• To understand the molecular mechanisms of kidney-specific and nephron-segment-specific expression of CLC-K channel genes, the rat ClC-K2 gene promoter was cloned and compared with that of CLC-K1 [3].
• Three new members, named ClC-K1, ClC-K2, ClC-3, have been isolated [4].

Other interactions of Clcnkb

• The 687-amino acid protein encoded by ClC-K2L is about 80% identical to rat ClC-K1 and about 40% identical to ClC-0, -1, and -2 [2].

Analytical, diagnostic and therapeutic context of Clcnkb

• Northern blot with total ClC-K2L as a probe under high stringency revealed its message predominantly in kidney, especially in the outer and inner medulla [2].
• Northern blot and immunohistochemistry showed that ClC-K1 and ClC-K2 are selectively expressed in the kidney, while ClC-3 distributes in a variety of organs such as brain, lung, and kidney [4].
• Dietary salt loading down-regulated CIC-K2 mRNA in the outer medulla 0.6-fold versus control whilst furosemide treatment, but not the low-salt diet, increased ClC-K2 mRNA in the outer (1.6-fold) and inner medulla (2.0-fold) [5].

References