We have previously demonstrated that mouse proximal tubules in vitro respond to changes in luminal flow with proportional changes in Na+ absorption (Du Z, Duan Y, Yan Q, Weinstein AM, Weinbaum S, and Wang T. Proc Natl Acad Sci USA 101: 13068-13073, 2004). It was hypothesized that brush-border microvilli function as a sensor to detect and amplify luminal hydrodynamic forces and transmit them to ...

A Na(+)-HCO3- coinflux carrier and the Na(+)-H+ antiport have both been shown to contribute to recovery from intracellular acidosis in cardiac tissue. We have investigated the participation of these mechanisms as well as metabolite (lactate and CO2) washout in the recovery of pHi after myocardial ischemia. Isovolumic ferret hearts were Langendorff-perfused with either HCO3(-)-buffered or nomina...

High-mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently, we demonstrated that HMGB1 inhibits HCO3 (-) absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolatera...

In humans and terrestrial vertebrates, the kidney controls systemic pH in part by absorbing filtered bicarbonate in the proximal tubule via an electrogenic Na+/HCO3- cotransporter (NBCe1/SLC4A4). Recently, human genetics revealed that NBCe1 is the major renal contributor to this process. Homozygous point mutations in NBCe1 cause proximal renal tubular acidosis (pRTA), glaucoma, and cataracts (I...

Hypercapnia is clinically defined as an arterial blood partial pressure of CO2 of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist-stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)...

Canalicular bile formation is a complex process that involves basolateral and apical cell membrane transport, paracellular transport and vesicular transport, all of which may be subject to regulation by pH. We review the concept that apical cell membrane bicarbonate secretion promotes bile salt independent canalicular bile formation. We show that the presence of paracellular electrolyte transpo...

During perfusion of a plasma-like solution, colonic absorption rate of chloride was much higher than the secretion rate of bicarbonate (34 vs. 3.5 meq/h, respectively). This might suggest that anion exchange (Cl/HCO3) accounts for only a small fraction of total chloride absorption. However, if the colon absorbs as well as secretes bicarbonate, this reasoning would underestimate the magnitude of...

The inner stripe of the outer medullary collecting tubule is a major distal nephron segment in urinary acidification. To examine the mechanism of basolateral membrane H+/OH-/HCO3- transport in this segment, cell pH was measured microfluorometrically in the inner stripe of the rabbit outer medullary collecting tubule perfused in vitro using the pH-sensitive fluorescent dye, (2',7')-bis(carboxyet...

Adenosine 3',5'-cyclic monophosphate stimulates chloride (Cl-) secretion across airway epithelia. To determine whether cAMP also stimulates HCO3- secretion, we studied cultured canine and human airway epithelial cells bathed in a HCO3-/CO2-buffered, Cl(-)-free solution. Addition of forskolin stimulated an increase in short-circuit current that was likely a result of bicarbonate secretion becaus...

Micropuncture techniques have been used to study electrolyte secretion by the spontaneously secreting in vitro rabbit pancreas over a wide range of environmental conditions. Pancreatic secretion does not have a strong requirement for HCO3 and secretion continues at nearly normal rates when exogenous HCO3 is replaced by acetate. Acetate concentration in the juice averages 70 meq/liter, nearly th...