Intercalated cell BK-α/β4 channels modulate sodium and potassium handling during potassium adaptation

J. David Holtzclaw, P. Richard Grimm, Steven C. Sansom

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


The large-conductance, calcium-activated potassium (BK) channels help eliminate potassium in mammals consuming potassium-rich diets. In the distal nephron, principal cells contain BK-α/β1 channels and intercalated cells contain BK-α/β4 channels. We studied whether BK-β4- deficient mice (Kcnmb4-/-) have altered renal sodium and potassium clearances compared with wild-type mice when fed a regular or potassium-rich diet for ten days. We did not detect differences in urinary flow or fractional excretions of potassium (FEK) or sodium (FENa) between Kcnmb4-deficient and wild-type mice fed a regular diet. However, a potassium-rich diet led to >4-fold increases in urinary flows for both groups of mice, although Kcnmb4-deficient mice exhibited less urinary flow, higher plasma potassium concentration, more fluid retention, and significantly lower FEK and FENa than wild-type mice despite similar plasma aldosterone levels. Immunohistochemical analysis revealed increased basolateral Na-KATPase in principal cells of all potassium-adapted mice, but expression of Na-K-ATPase in intercalated cells was >10-fold lower. The size of intercalated cells reduced and luminal volume increased among potassium-adapted wild-type but not Kcnmb4-deficient mice. Paradoxically, this led to increased urinary fluid velocity in potassium-adapted Kcnmb4-deficient mice compared with wild-type mice. Taken together, these data suggest that BK-α/β4 channels in intercalated cells reduce cell size, increasing luminal volume to accommodate higher distal flow rates during potassium adaptation. These changes streamline flow across the principal cells, producing gradients more favorable for potassium secretion and less favorable for sodium reabsorption.

Original languageEnglish (US)
Pages (from-to)634-645
Number of pages12
JournalJournal of the American Society of Nephrology
Issue number4
StatePublished - Apr 2010
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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