Autosomal dominant distal renal tubular acidosis in two pediatric patients with mutations in the SLC4A1 gene. Can the maximum urinary pCO test be normal?

Primary distal renal tubular acidosis (dRTA) is a rare tubulopathy characterised by the presence of hyperchloremic metabolic acidosis. It is caused by the existence of a defect in the function of the H -ATPase located on the luminal side of the α-intercalated cells or the Cl HCO3 (AE1) anion exchanger located on the basolateral side. Patients do not acidify the urine after acid overload (NH4Cl) or after stimulating H secretion by obtaining a high intratubular concentration of an anion such as chlorine (pH is measured) or HCO3- (urinary pCO is measured).

Vasopressin acts as a synapse organizer in limbic regions by boosting PSD95 and GluA1 expression.

Hypothalamic arginine vasopressin (AVP)-containing magnocellular neurosecretory neurons (AVPMNN) emit collaterals to synaptically innervate limbic regions influencing learning, motivational behaviour, and fear responses. Here, we characterize the dynamics of expression changes of two key determinants for synaptic strength, the postsynaptic density (PSD) proteins AMPAR subunit GluA1 and PSD scaffolding protein 95 (PSD95), in response to in vivo manipulations of AVPMNN neuronal activation state, or exposure to exogenous AVP ex vivo. Both long-term water deprivation in vivo, which powerfully upregulates AVPMNN metabolic activity, and exogenous AVP application ex vivo, in brain slices, significantly increased GluA1 and PSD95 expression as measured by western blotting, in brain regions reportedly receiving direct ascending innervations from AVPMNN (i.

Identification of a unique endoplasmic retention motif in the Xenopus GIRK5 channel and its contribution to oocyte maturation.

G protein-activated inward-rectifying potassium (K ) channels (Kir3/GIRK) participate in cell excitability. The GIRK5 channel is present in Xenopus laevis oocytes. In an attempt to investigate the physiological role of GIRK5, we identified a noncanonical di-arginine endoplasmic reticulum (ER) retention motif (KRXY).

Metabolic acidosis and hyperkalemia differentially regulate cation HCN3 channel in the rat nephron.

The kidney controls body fluids, electrolyte and acid-base balance. Previously, we demonstrated that hyperpolarization-activated and cyclic nucleotide-gated (HCN) cation channels participate in ammonium excretion in the rat kidney. Since acid-base balance is closely linked to potassium metabolism, in the present work we aim to determine the effect of chronic metabolic acidosis (CMA) and hyperkalemia (HK) on protein abundance and localization of HCN3 in the rat kidney.

"Funny" channels in cardiac mitochondria modulate membrane potential and oxygen consumption.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by a family of four genes (HCN1-4). All isoforms are expressed in the heart, HCN4 being the most abundant in the sinoatrial node (SAN). HCN channels are responsible for the "funny" current (I) associated with the generation and autonomic control of the diastolic depolarization phase of cardiac action potential.

Novel Potassium Channels in Kidney Mitochondria: The Hyperpolarization-Activated and Cyclic Nucleotide-Gated HCN Channels.

Hyperpolarization-activated cationic HCN channels comprise four members (HCN1-4) that control dendritic integration, synaptic transmission and action potential firing. In the kidney, HCN1, HCN2 and HCN3 are differentially expressed and contribute to the transport of sodium, potassium (K) and ammonium into the nephrons. HCN3 is regulated by K diets in the kidney.

Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families.

Background: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare disease characterized by a hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitraturia, nephrocalcinosis, and conserved glomerular filtration rate. In some cases, neurosensorial deafness is associated. dRTA is developed during the first months of life and the main manifestations are failure to thrive, vomiting, dehydration, and anorexia.

Extracellular Cl(-) regulates human SO4 (2-)/anion exchanger SLC26A1 by altering pH sensitivity of anion transport.

Genetic deficiency of the SLC26A1 anion exchanger in mice is known to be associated with hyposulfatemia and hyperoxaluria with nephrolithiasis, but many aspects of human SLC26A1 function remain to be explored. We report here the functional characterization of human SLC26A1, a 4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid (DIDS)-sensitive, electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, bicarbonate, thiosulfate, and (with divergent properties) chloride. Human SLC26A1-mediated anion exchange differs from that of its rodent orthologs in its stimulation by alkaline pHo and inhibition by acidic pHo but not pHi and in its failure to transport glyoxylate.

Immunolocalization of hyperpolarization-activated cationic HCN1 and HCN3 channels in the rat nephron: regulation of HCN3 by potassium diets.

Hyperpolarization-activated cationic and cyclic nucleotide-gated channels (HCN) comprise four homologous subunits (HCN1-HCN4). HCN channels are found in excitable and non-excitable tissues in mammals. We have previously shown that HCN2 may transport ammonium (NH4 (+)), besides sodium (Na(+)), in the rat distal nephron.

Differential expression of the Kv1 voltage-gated potassium channel family in the rat nephron.

Several potassium (K(+)) channels contribute to maintaining the resting membrane potential of renal epithelial cells. Apart from buffering the cell membrane potential and cell volume, K(+) channels allow sodium reabsorption in the proximal tubule (PT), K(+) recycling and K(+) reabsorption in the thick ascending limb (TAL) and K(+) secretion and K(+) reabsorption in the distal convoluted tubule (DCT), connecting tubule (CNT) and collecting duct. Previously, we identified Kv.

The polarization of the G-protein activated potassium channel GIRK5 to the vegetal pole of Xenopus laevis oocytes is driven by a di-leucine motif.

The G protein-coupled inwardly-rectifying potassium channels (known as GIRK or Kir3) form functional heterotetramers gated by G-βγ subunits. GIRK channels participate in heart rate modulation and neuronal postsynaptic inhibition in mammals. In Xenopus laevis oocytes, GIRK5 is a functional homomultimer.

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

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.

Potassium secretion by voltage-gated potassium channel Kv1.3 in the rat kidney.

The fine regulation of Na(+) and K(+) transport takes place in the cortical distal nephron. It is well established that K(+) secretion occurs through apical K(+) channels: the ROMK and the Ca(2+)- and voltage-dependent maxi-K. Previously, we identified the voltage-gated Kv1.

Peptide sr11a from Conus spurius is a novel peptide blocker for Kv1 potassium channels.

More than a hundred conotoxins are known today and from them, only seven conopeptides have been identified to target voltage-gated potassium channels (Kv). Conotoxin sr11a belongs to the I(2)-superfamily which is characterized by four disulfide bridges and provokes muscle stiffness when injected intracranially in mice. The aim of this work was to test the biological activity of sr11a on recombinant voltage-gated Kv1 potassium channels expressed in Xenopus laevis oocytes.

Expression and immunolocalization of ERG1 potassium channels in the rat kidney.

Potassium (K(+)) channels participate in K(+) secretion, K(+) recycling, and cell volume regulation and help to maintain the resting potential in mammalian kidneys. Previously, we identified a set of voltage-gated K(+) channels (Kv1) in the inner medullary collecting duct of the rat kidney. In the present work, we identified the voltage-gated K(+) channel ether-à-go-go-related gene (ERG) in the rat kidney.

Phosphorylation of a tyrosine at the N-terminus regulates the surface expression of GIRK5 homomultimers.

The G protein-coupled inwardly rectifying GIRK5 and Delta5GIRK5 splicing variants do not express functional potassium channels. In contrast, Delta25GIRK5 forms functional homomultimers in Xenopus laevis oocytes. A tyrosine is present at the N-term of the non-functional isoforms.

A voltage-gated K(+) current in renal inner medullary collecting duct cells.

We studied the K(+)-selective conductances in primary cultures of rat renal inner medullary collecting duct (IMCD) using perforated-patch and conventional whole cell techniques. Depolarizations above -20 mV induced a time-dependent outward K(+) current (I(vto)) similar to a delayed rectifier. I(vto) showed a half-maximal activation around 5.

Basal activity of GIRK5 isoforms.

G protein-coupled inwardly rectifying K(+) channels (GIRK or Kir3) form functional heterotetramers gated by Gbetagamma subunits. GIRK channels are critical for functions as diverse as heart rate modulation and neuronal post-synaptic inhibition. GIRK5 (Kir3.