I recently saw an interesting case of Familial Hyperkalemic Hypertension ( Gordon's Syndrome ) and read the current literature and role of WNK family of proteins. With-no-Lysine (K) kinases are family of proteins that have been found to play an important role in epithelial ions transport. They are involved in signaling in the sodium chloride and potassium transport in the aldosterone sensitive distal nephron. It is little bit complicated, but the figure will be easy to follow.
1.WNK4 inhibits NCC and ROMK
2.WNK1 stimulates ENaC and NCC through different mechanisms. Former through SGK-1 (Serum Glucocorticoid Kinase) and latter through inhibiting effect on WNK-4
3.Both WNK4 and WNK1 act synergistically to inhibit ROMK channel.
4.KS-WNK1 suppress NCC transport via its dominant negative effect on WNK1, stimulates ROMK activity via the same antagonistic mechanism and enhances ENaC-mediated transport through a different process
These observations suggest that, under certain physiologic circumstances, aldosterone simultaneouly downregulates electroneutral transport via NCC and enhances electrogenic transport via ENaC and ROMK
Gordon's syndrome is caused by mutations in WNK4 and WNK1 causing overactivity of NCC and inhibiting ROMK leading to hypertension and hyperkalemia. Other associated features are hypercalciuria and distal RTA, suggesting that atleast a subset of patients carry essentially a phenotype that is essentially a "mirror image" of Gietelman's Syndrome. The best way to remember these 2 syndromes is to be familiar with the features of thiazides.
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