Abstract

NHERF‐1 regulates several ion transporters in kidney proximal tubules including NHE3, NpT2a, NBC, CFTR, and Na‐K ATPase (NKA) through modulation of protein complex formation and through modulation of hormone receptor signaling, in particular, PTH and dopamine. Regulation of ion balance changes with aging; however, the expression of NHERF‐1 in aging has not been studied. We hypothesize that loss of NHERF‐1 regulation of NHE3 and NKA with aging contributes to alterations in maintenance of sodium balance. To address this hypothesis, we compared expression of NHERF‐1, NHE3, and NKA in kidneys from young (4 m old) and old (24 m old) female F344 rats by western blot in isolated apical and basolateral membranes and by immunohistochemistry. Western blot showed complete loss of NHERF‐1 in both apical and basolateral membranes from kidneys of 24 m old rats. NKA expression significantly decreased in 24 m old rats as compared to 4 m old rats, but NHE3 expression did not change with aging. Similar to aging, NHERF‐1 expression was also found to be absent in proximal tubule cells from spontaneous hypertensive rats. These data suggest that in SHR and aging dependent alterations in ion homeostasis may result from changes in transporter expression and from loss of normal hormonal regulatory pathways. Supported by AHA and VAGrant Funding Source: AHA, VA

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