The hyperpolarization-activated cyclic nucleotide-gated HCN2 channel transports ammonium in the distal nephron

Rolando Carrisoza-Gaytán, Claudia Rangel, Carolina Salvador, Ricardo Saldaña-Meyer, Christian Escalona, Lisa M. Satlin, Wen Liu, Beth Zavilowitz, Joyce Trujillo, Norma A. Bobadilla, Laura I. Escobar

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Recent studies have identified Rhesus proteins as important molecules for ammonia transport in acid-secreting intercalated cells in the distal nephron. Here, we provide evidence for an additional molecule that can mediate NH3/NH4 excretion, the subtype 2 of the hyperpolarization-activated cyclic nucleotide-gated channel family (HCN2), in collecting ducts in rat renal cortex and medulla. Chronic metabolic acidosis in rats did not alter HCN2 protein expression but downregulated the relative abundance of HCN2 mRNA. Its cDNA was identical to the homolog from the brain and the protein was post-translationally modified by N-type glycosylation. Electrophysiological recordings in Xenopus oocytes injected with HCN2 cRNA found that potassium was transported better than ammonium, each of which was transported significantly better than sodium, criteria that are compatible with a role for HCN2 in ammonium transport. In microperfused rat outer medullary collecting duct segments, the initial rate of acidification, upon exposure to a basolateral ammonium chloride pulse, was higher in intercalated than in principal cells. A specific inhibitor of HCN2 (ZD7288) decreased acidification only in intercalated cells from control rats. In rats with chronic metabolic acidosis, the rate of acidification doubled in both intercalated and principal cells; however, ZD7288 had no significant inhibitory effect. Thus, HCN2 is a basolateral ammonium transport pathway of intercalated cells and may contribute to the renal regulation of body pH under basal conditions.

Original languageEnglish
Pages (from-to)832-840
Number of pages9
JournalKidney International
Volume80
Issue number8
DOIs
StatePublished - 2 Oct 2011

Keywords

  • acid-base homeostasis
  • ammonium
  • collecting duct
  • hyperpolarization-activated cyclic nucleotide-gated channel
  • intercalated cell

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