Effects of insulin on Na and K transporters in the rat CCD.

We tested the effects of insulin (2 nM, 30-60 min) on principal cells of isolated split-open rat cortical collecting ducts (CCD) using whole-cell current measurements. Insulin addition to the superfusate of the tubules enhanced Na pump (ouabain-sensitive) current from 18 ± 3 to 31 ± 3 pA/cell in control and from 74 ± 9 to 126 ± 11 pA/cell in high K-fed animals. It also more than doubled ROMK (tertiapin-Q-sensitive) K(+) currents in control CCD from 320 ± 40 to 700 ± 80 pA/cell, although it did not affect this current in tubules from K-loaded rats.

Potassium excretion during antinatriuresis: perspective from a distal nephron model.

Renal excretion of Na(+) and K(+) must be regulated independently within the distal nephron, but is complicated by the fact that changing excretion of one solute requires adjustments in the transport of both. It is long known that hypovolemia increases Na(+) reabsorption while impairing K(+) excretion, even when distal Na(+) delivery is little changed. Renewed interest in this micropuncture observation came with identification of the molecular defects underlying familial hyperkalemic hypertension (FHH), which also increases distal Na(+) reabsorption and impairs K(+) excretion.

Regulation of epithelial Na+ channels by adrenal steroids: mineralocorticoid and glucocorticoid effects.

Epithelial Na+ channels (ENaC) can be regulated by both mineralocorticoid and glucocorticoid hormones. In the mammalian kidney, effects of mineralocorticoids have been extensively studied, but those of glucocorticoids are complicated by metabolism of the hormones and cross-occupancy of mineralocorticoid receptors. Here, we report effects of dexamethasone, a synthetic glucocorticoid, on ENaC in the rat kidney.

Effects of dietary K on cell-surface expression of renal ion channels and transporters.

Changes in apical surface expression of ion channels and transporters in the superficial rat renal cortex were assessed using biotinylation and immunoblotting during alterations in dietary K intake. A high-K diet increased, and a low-K diet decreased, both the overall and surface abundance of the β- and γ-subunits of the epithelial Na channel (ENaC). In the case of γ-ENaC, the effect was specific for the 65-kDa cleaved form of the protein.

Flow-dependent transport in a mathematical model of rat proximal tubule.

The mathematical model of rat proximal tubule has been extended to include calculation of microvillous torque and to incorporate torque-dependent solute transport in a compliant tubule. The torque calculation follows that of Du Z, Yan Q, Duan Y, Weinbaum S, Weinstein AM, and Wang T (Am J Physiol 290: F289-F296, 2006). In the model calculations, torque-dependent scaling of luminal membrane transporter density [either as an ensemble or just type 3 Na(+)/H(+) exchanger (NHE3) alone] had a relatively small impact on overall Na(+) reabsorption and could produce a lethal derangement of cell volume; coordinated regulation of luminal and peritubular transporters was required to represent the overall impact of luminal flow on Na(+) reabsorption.

Na channel expression and activity in the medullary collecting duct of rat kidney.

The expression and activity of epithelial Na(+) channels (ENaC) in the medullary collecting duct of the rat kidney were examined using a combination of whole cell patch-clamp measurements of amiloride-sensitive currents (I(Na)) in split-open tubules and Western blot analysis of alpha-, beta-, and gamma-ENaC proteins. In the outer medullary collecting duct, amiloride-sensitive currents were undetectable in principal cells from control animals but were robust when rats were treated with aldosterone (I(Na) = 960 +/- 160 pA/cell) or fed a low-Na diet (I(Na) = 440 +/- 120 pA/cell). In both cases, the currents were similar to those measured in principal cells of the cortical collecting duct from the same animals.

High-conductance K channels in intercalated cells of the rat distal nephron.

High-conductance (BK or maxi) K(+) channels were observed in cell-attached patches of the apical membrane of the isolated split-open rat connecting tubule (CNT). These channels were quite rare in cells identified visually as principal cells (PCs; 5/162 patches) but common in intercalated cells (ICs; 24/26 patches). The BK-expressing intercalated cells in the CNT and cortical collecting duct (CCD) were characterized by a low membrane potential (-36 mV) under short-circuit conditions, measured from the reversal potential of the channel currents with similar K(+) concentrations on both sides of the membrane.

Cl- channels of the distal nephron.

Cl- currents were observed under whole cell clamp conditions in cells of the rat cortical collecting duct (CCD), connecting tubule (CNT), and thick ascending limb of Henle's loop (TALH). These currents were much larger in intercalated cells compared with principal cells of the CCD and were also larger in the TALH and in the CNT compared with the CCD. The conductance had no strong voltage dependence, and steady-state currents were similar in inward and outward directions with similar Cl- concentrations on both sides of the membrane.

CT screening for lung cancer: prevalence and incidence of mediastinal masses.

Purpose: To determine the frequency and natural course of mediastinal masses in asymptomatic people at high risk for lung cancer who were undergoing computed tomographic (CT) screening.

Materials And Methods: Informed consent and institutional review board approval for this HIPAA-compliant study were obtained at each participating institution. All documented mediastinal masses among the 9263 baseline and 11 126 annual repeat screenings performed in the Early Lung Cancer Action Project (ELCAP) and its successor project, the New York ELCAP, were identified.

Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection.

Based on the role of tumor necrosis factor-alpha (TNF-alpha) in ischemic preconditioning (IPC) and the age-associated loss of both TNF-alpha-induced platelet-derived growth factor-AB (PDGF-AB)-mediated cardioprotection and IPC-mediated cardioprotection, we hypothesized that targeting of PDGF-AB-based pathways would restore cardioprotection by IPC in the aging heart. To study this, IPC was induced in 4- and 24-mo-old F344 rats. Sections of young hearts isolated 1 day post-IPC revealed increased TNF-alpha compared with controls.

A mathematical model of rat distal convoluted tubule. I. Cotransporter function in early DCT.

A model of rat early distal convoluted tubule (DCT) is developed in conjunction with a kinetic representation of the thiazide-sensitive NaCl cotransporter (TSC). Realistic constraints on cell membrane electrical conductance require that most of the peritubular Cl(-) reabsorption proceeds via a KCl cotransporter,along with most of the K(+) recycled from the Na-K-ATPase. The model tubule reproduces the saturable Cl(-) reabsorption of DCT but not the micropuncture finding of linear Na(+) flux in response to load, more likely a feature of late DCT (CNT).

Basolateral K+ conductance in principal cells of rat CCD.

Whole cell K+ current was measured by forming seals on the luminal membrane of principal cells in split-open rat cortical collecting ducts. The mean inward, Ba2+-sensitive conductance, with 40 mM extracellular K+, was 76 +/- 12 and 141 +/- 22 nS/cell for animals on control and high-K+ diets, respectively. The apical contribution to this was estimated to be 3 and 16 nS/cell on control and high-K+ diets, respectively.

Na channels in the rat connecting tubule.

Epithelial Na channels were investigated using patch-clamp techniques in connecting tubule (CNT) segments isolated from rat kidney. Cell-attached patches with Li+ in the patch pipette contained channels with conductances for inward currents of 13-16 pS and slow opening and closing kinetics, similar to properties of Na channels in the cortical collecting tubule (CCT). Macroscopic amiloride-sensitive currents (INa) were also observed under whole cell clamp conditions.

Mineralocorticoid regulation of epithelial Na+ channels is maintained in a mouse model of Liddle's syndrome.

Currents through epithelial Na channels (ENaCs) were measured in the cortical collecting tubule (CCT) of mice expressing truncated beta-subunits of ENaC, reproducing one of the mutations found in human patients with Liddle's syndrome. Tubules were isolated from mice homozygous for the Liddle mutation (L/L) and from wild-type (WT) littermates. Amiloride-sensitive currents (INa) from single cells were recorded under whole cell clamp conditions.