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

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