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. Author manuscript; available in PMC: 2016 Nov 1.
Published in final edited form as: Pflugers Arch. 2015 Apr 24;467(11):2235–2241. doi: 10.1007/s00424-015-1708-2

Fig. 2.

Fig. 2

Model illustrating WNK1 and WNK4 both contribute to stimulation of NCC via OSR1/SPAK. This model is based on results of multiple studies performed in vivo showing that gain-of-function of WNK1 or WNK4 stimulates NCC and loss-of-function of WNK4 or SPAK inhibits NCC. The role of WNK3 in vivo remains to be defined. The precise relationship between WNK1 and WNK4 regulation of NCC is also unknown, but is likely positive (i.e., mathematically additive, sub-additive or synergistic) rather than antagonistic toward to each other (see text for details). Similarly, WNK1 and 4 likely also both contribute to stimulation of NKCC2 in TAL via OSR1/SPAK (not shown).