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Circadian expression of H,K‐ATPase type 2 contributes to the stability of plasma K+ levels
Author(s) -
Crambert Gilles,
Centeno Gabriel,
Firsov Dmitri,
Salhi Amel
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1103.1
Subject(s) - circadian rhythm , medicine , endocrinology , homeostasis , excretion , kidney , period (music) , urinary system , biology , chemistry , physics , acoustics
Maintenance by the kidney of stable plasma K+ values is crucial, as the latter control muscle and nerve activity. Inability to do so, induced hyper‐ or hypokalemia both related to heart dysfunctions, muscle weakness and neurological disorders. Since renal K+ excretion is regulated by the circadian clock we aimed to identify the ion transporters involved in this process. In control mice, the renal mRNA expression of the H,K‐ATPase type 2 (HKA2) is 25% higher during rest compared to the activity period. Conversely, under dietary K+ restriction, HKA2 expression is ~ 40% higher during the activity period. This reversal suggests that HKA2 contributes to the circadian regulation of K+ homeostasis. Compared to their wild‐type littermate (WT), HKA2‐ null mice on a normal diet have a 2‐fold higher K+ renal excretion during rest. Under K+ restriction, their urinary K+ loss is 40% higher during the activity period. This inability to excrete K+ “on time” is reflected in plasma K+ values, which vary by 12 % between activity and rest periods in HKA2‐null mice but remain stable in WT. Analysis of the circadian expression of HKA2 regulators suggests that Nrf2 but not progesterone contributes to its rhythmicity. Therefore, HKA2 acts to maintain the circadian rhythm of urinary K+ excretion and preserve stable plasma K+ values throughout the day.