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R S Balaban

Publications and source records attributed to R S Balaban.

176 records · Page 10Linked to original sources
PubMed1980

Coupling of active ion transport and aerobic respiratory rate in isolated renal tubules.

We report the results of studies in which the cytoplasmic coupling between Na+,K+-ATPase activity (presumably a measure of active transport) and the mitochondrial respiratory rate was investigated in a tubule suspension from the rabbit kidney cortex. Simultaneous measurements of the redox state of mitochondrial nicotinamide adenine dinucleotide (NAD) (performed fluorometrically), the cellular ATP and ADP concentrations, and the oxygen consumption rate (QO2) were made under conditions known to alter the Na+,K+-ATPase turnover. Ouabain (25 microM) caused: (i) a 54% inhibition of QO2, (ii) a net reduction of NAD, and (iii) a 30% increase in the ATP/ADP ratio. The addition of K+ (5 ?M) to K+-depleted tubules caused: (i) an initial 127% stimulation of QO2 followed by a new steady-state QO2 50% above control, (ii) an initial large oxidation of NAD followed by a new steady state more oxidized than the control level, and (iii) a 47% decrease in the cellular ATP/ADP ratio. These data indicate that the cellular ATP and ADP concentrations or the ATP/ADP ratio may be part of the coupling mechanism linking Na+,K+-ATPase turnover and the aerobic metabolic rate in kidney.

Adenosine Diphosphate↗
PubMed1980

Coupling of aerobic metabolism to active ion transport in the kidney.

1. The redox state of mitochondrial NAD was monitored fluorometrically as a function of active ion transport work in the isolated doubly perfused bullfrog kidney. 2. Initial experiments to measure the O2 consumption (QO2) of small pieces from the bullfrog kidney gave a basal QO2 - 3.0 (+/- 0.43) nmoles O2/mg dry wt. min. Addition of 50 microM-ouabain inhibited QO2 by 72.7%. Subsequent addition of the mitochondrial uncoupler 1799 stimulated QO2 by 226%, while cyanide totally inhibited respiration. 3. Ion transport functional parameters and NADH fluorescence were simultaneously monitored during systematic reductions in perfusate PO2 to test the sufficiency of O2 delivery to the isolated perfused frog kidney. No significant changes in transport functions or fluorescence were observed until the PO2 dropped to 184 mm Hg or below. O2 tensions of 184 mm Hg or below caused decreases in G.F.R. and transport functions which were accompanied by an increase in NADH fluorescence. The lack of changes in kidney function in the PO2 range 550-340 mmHg suggested that the tissue is adequately oxygenated at the normal perfusate PO2 of 550 mmHg. 4. The relationship between active transport rate and NAD redox levels was studied by increasing transport work (via increased G.F.R. or ADH) or by decreasing transport work (via decreased G.F.R. or ouabain) while simultaneously monitoring the NAD redox state of the intact tissue fluorometrically. In all cases, an increase in work caused a net oxidation of NAD while a decrease in work caused a reduction of NAD. 5. It is concluded that the NADH fluorescence responses are indicative of mitochondrial active to passive transitions in response to changes in active transport work. The aerobic production of ATP and the normally functioning Na-K-ATPase appear to be essential to maintain active transport and to elicit the appropriate state transitions. Thus, ATP (and, possibly, ADP and Pi) may be part of the coupling mechanism linking active ion transport and aerobic metabolic rate in the kidney.

Absorption↗
PubMed1980

Improved renal cortical tubule suspension: spectrophotometric study of O2 delivery.

An improved cortical tubule suspension from the rabbit kidney is described that contains almost entirely proximal convoluted tubules with little contamination by cellular debris or glomeruli. These tubules appear to be capable of active transepithelial transport, since their tubular lumina are open and ouabain inhibits 70% of the QO2. In previous preparations with closed tubular lumina, ouabain inhibited QO2 only 40% and the base-line QO2 was one-half to one-quarter that of the present preparation. The delivery of oxygen to this tubule suspension was compared to that of slices by three different means: oxygen consumption kinetics, ATP content, and, more directly by spectrophotometric monitoring of the redox state of cytochrome oxidase. Results demonstrate that the cortical slice is evidently oxygen deficient even when the bath PO2 is in excess of 570 mmHg. In contrast, the tubule suspension is shown to be adequately oxygenated even at a bath PO2 of 10 mmHg. This tubule suspension will be highly applicable for the analysis of aerobic metabolism in a functionally intact renal preparation by optical, electrode, and biochemical assay technologies.

Adenosine Triphosphate↗
PubMed1980

Inhibition of Renal Metabolism. Relative effects of arsenate on sodium, phosphate, and glucose transport by the rabbit proximal tubule.

These studies examine the inhibitory effects of arsenate on the transport of sodium, phosphate, glucose, and para-aminohippurate (PAH) as well as oxidative metabolism by proximal convoluted tubules from the rabbit kidney. Transport rates were measured with radioisotopes in isolated and perfused segments. Metabolic activity was monitored through oxygen-consumption rates and HADH fluorescence in parallel studies in suspensions of cortical tubules. The addition of 1mM arsenate to the perfusate reduced fluid absorption rates from 1.24 +/- 0.17 to 0.66 +/- 0.19 nl/nm.min (P < 0.01) and lumen-to-bath phosphate transport from 9.93 +/- 3.47 to 4.25 +/- 1.08 pmol/mm.min (P < 0.01). Similar concentrations of arsenate reduced glucose transport only slightly from 66.1 +/- 6.0 to 56.8 +/-4 4.6 pmol/mm.min (P < 0.05) and had no effect of PAH secretion. Removing phosphate from the perfusate did not affect the net transport of sodium or glucose. In suspensions of tubules, arsenate increased oxygen consumption rates by 20.5 +/- 2.9% and decreased NADH fluorescence by 10.8 +/- 1.5%. These effects on metabolism were concentration dependent and magnified in the presence of ouabain. The data indicate that arsenate's main effect is to uncouple oxidative phosphorylation, and that graded uncoupling of oxidative metabolism causes graded reductions in the net transport of both sodium and phosphate. Glucose transport is inhibited only slightly and PAH secretion is not affected. Thus, partial as opposed to complete inhibition of metabolism reveals that different relationships exist between net sodium transport and the transport of phosphate, glucose, and PAH by the proximal renal tubule.

Animals↗
PubMed1979

On the cross-reactivity of amiloride and 2,4,6 triaminopyrimidine (TAP) for the cellular entry and tight junctional cation permeation pathways in epithelia.

2,4,6 Triaminopyrimidine (TAP) has been previously shown to inhibit the passive tight junctional cation permeation pathway in various "leaky" epithelia. Amiloride has been shown to be an effective inhibitor of the cation cellular entry pathway in "tight" epithelia. In this paper we demonstrate that TAP and amiloride at appropriate concentrations are able to block either of these epithelial cation permeation pathways. TAP was found to block the Na entry pathway in frog skin with the following characteristics: it (1) inhibits from the external solution only, (2) is completely reversible, (3) increases the transepithelial resistance, (4) is active in the monoprotonated form, (5) is noncompetitive with Na, (6) displays saturation kinetics which obey a simple kinetic model (KI = 1 X 10(-3) M), (7) is independent of external calcium, (8) is dependent on external buffering capacity, and (9) is competitive with amiloride. Amiloride inhibition of the junctional permeation in gallbladder had the following characteristics: it (1) increases the transepithelial resistance, (2) decreases cation conductance without affecting the anion conductance, (3) displays saturation kinetics which obey a simple kinetic model (KI = 1 X 10(-3) M), and (4) possesses inhibitory activity in both its protonated and unprotonated form. These results not only indicate that a similar inhibitory site may exist in both of these cation permeation pathways, but also provide information on the chemical nature and possible location of these inhibitory sites.

Amiloride↗
PubMed1979

Comparison of the effects of increased intracellular calcium and antidiuretic hormone on active sodium transport in frog skin. A study with the calcium ionophore A23187.

The addition of the Ca2+ ionophore A23187 (1 microM) to the inside solution of the frog skin resulted in an approx. 40% transient increase in the active influx of Na+ and ionic conductance, which decayed to an approx. 13% steady-state stimulation after 1--2 h. A23187 had no effect from the outside solution. A23187's stimulatory action is most likely the result of the ionophore's ability to increase intracellular Ca2+. This contention is supported by the following experimental results: (1) reintroduction of Ca2+ into a Ca2+-free inner solution stimulated Na+ transport only in the presence of A23187: (2) Mg2+ would not mimic these effects, and (3) EGTA in the inner solution would inhibit the A23187 response. The stimulation of active transport and ionic conductances elicited by A23187 were found to be very similar to those caused by antidiuretic hormone. Several lines of evidence suggest that A23187 may by-pass steps in the normal antidiuretic hormone stimulatory process: (1) A23187 and antidiuretic hormone are apparently non-additive; (2) A23187 acts three times faster than antidiuretic hormone; (3) A23187 stimulates antidiuretic hormone-insensitive frog skins, and (4) results from other laboratories indicate that A23187 does not increase cyclic AMP concentrations. It is speculated that an increase in free intracellular Ca2+ may be a step in the normal antidiuretic hormone stimulatory process. This increase in intracellular Ca2+ may in turn stimulate active sodium transport by increasing the Na+ permeability of the outer 'rate-limiting' membrane.

Animals↗
PubMed1979

On the mechanism of the amiloride-sodium entry site interaction in anuran skin epithelia.

The steady-state transport kinetics of the interaction between external sodium and the diuretic drug, amiloride, was studied in isolated anuran skin epithelia. We also investigated the effect of calcium on the amiloride-induced inhibition of short-circuit current (Isc) in these epithelial preparations. The major conclusions of this study are: (a) amiloride is a noncompetitive inhibitor of Na entry in bullfrog and grassfrog skin, but displays mixed inhibition in R. temporaria and the toad. A hypothesis which states that the interaction sites for amiloride and Na on the putative entry protein are spatially distinct in all of these species is proposed. (b) The stoichiometry of interaction between amiloride and the Na entry mechanism is not necessarily one-to-one. (c) The external Ca requirement for the inhibitory effect of amiloride is not absolute. Amiloride, at all concentrations, is equally effective in inhibiting Isc of bullfrog skin independently from the presence or absence of external Ca.

Amiloride↗
PubMedDate not supplied

The effect of off-resonance radiofrequency pulse saturation on fMRI contrast.

This paper describes the use of off-resonance saturation to further manipulate the blood oxygenation level dependent (BOLD) contrast of fMRI. A customized narrow bandwidth radiofrequency pulse, applied with a range of frequency offsets prior to selection of each slice, was designed and incorporated into a gradient echo EPI sequence. This application takes advantage of the resonance frequency and linewidth differences between the oxygenated and deoxygenated state of blood in human brain during task activation and rest, and is capable of creating an enhancement in the contrast of the BOLD effect. Because of a possible contribution to the signal change from cerebro-spinal fluid, which has a much narrower linewidth and smaller frequency shift compared with the brain tissue, data were also collected using a nulling inversion pulse. The inversion pulse was applied before the off-resonance pulse and data acquisition to eliminate the CSF signal. Functional areas are thus more localized to the brain tissue.

Brain↗
PubMedDate not supplied

Radiofrequency shielding of surface coils at 4.0 T.

Because radiation loss associated with a radiofrequency (RF) coil increases as roughly the fourth power of the frequency, this loss mechanism may become important in high-field studies above 2.0 T. In this study, the contribution of radiation losses at 4.0 T were determined in a rectangular surface coil using an RF shield to modify the radiation losses. The effect of this shield was determined on coil Q, B1 distribution, and signal to noise as a function of distance between the coil and the shield. Phantoms and human tissue were evaluated to characterize the loss mechanisms. The results demonstrate a large radiation loss in the unshielded surface coil. However, the radiation losses in vivo were not dominant owing to a large inductive loss occurring from dielectric currents in the body at 170 MHz.

Artifacts↗
PubMedDate not supplied

Using cardiac phase to order reconstruction (CAPTOR): a method to improve diastolic images.

A method is proposed to reconstruct multiphase images that accurately depicts the entire cardiac cycle. A segmented, gradient-recalled-echo sequence (FASTCARD) was modified to acquire data continuously. Images were reconstructed retrospectively by selecting views from each heartbeat based on cardiac phase rather than the time elapsed from the QRS complex. Cardiac phase was calculated using a model that compensates for beat-to-beat heart rate changes. Images collected using cardiac phase to order reconstruction (CAPTOR) depict the entire cardiac cycle and lack the temporal gap that is characteristic of prospectively reconstructed sequences. Time-volume curves of the left ventricle capture the contribution of atrial contraction to end-diastolic volume (EDV). Transmitral phase-contrast flow measurements show a second peak inflow (alpha wave) that is absent in the standard sequence. Because atrial contraction contributes to ventricular EDV, images using CAPTOR potentially may provide a more reliable measure of EDV, stroke volume, and ejection fraction than standard techniques.

Cardiac Volume↗
PubMedDate not supplied

Centric ordering is superior to gradient moment nulling for motion artifact reduction in EPI.

Echo-planar imaging (EPI) is sensitive to motion despite its rapid data acquisition rate. Compared with traditional imaging techniques, it is more sensitive to motion or flow in the phase-encode direction, which can cause image artifacts such as ghosting, misregistration, and loss of spatial resolution. Consequently, EPI of dynamic structures (eg, the cardiovascular system) could benefit from methods that eliminate these artifacts. In this paper, two methods of artifact reduction for motion in the phase-encode direction are evaluated. First, the k-space trajectory is evaluated by comparing centric with top-down ordered sequences. Next, velocity gradient moment nulling (GMN) of the phase-encode direction is evaluated for each trajectory. Computer simulations and experiments in flow phantoms and rabbits in vivo show that uncompensated centric ordering produces the highest image quality. This is probably due to a shorter readout duration, which reduces T2* relaxation losses and off-resonance effects, and to the linear geometry of phantoms and vessels, which can obscure centric blurring artifacts.

Animals↗
PubMedDate not supplied

Reduction of field of view in MRI using a surface-spoiling local gradient insert.

Herein is presented a method for suppressing the magnetic resonance signal to a controlled depth by applying a spatially heterogeneous spoiler field between the slice-select and readout pulses. Eliminating the signal from near-surface regions allows one to shrink the field of view without introducing aliasing artifacts, thereby decreasing imaging time over a smaller defined volume. A unique planar magnetic gradient coil was constructed to generate the spoiler field. Phantom and human subject studies showed that the signal can be suppressed to controlled distances of up to 90 mm from the coil, with modest requirements on power supplies, pulse sequences, and materials, and with no increase in imaging time.

Artifacts↗
PubMedDate not supplied

Current topic: transport mechanisms in preimplantation mammalian embryos.

The main theme of this brief review article is that the study of membrane transport from a developmental point of view can be equated with the study of regulation. Although the blastocyst develops primarily under the control of the genetic information it inherits, it may also need maternal signals at critical stages. The study of blastocyst physiology is thus relevant to understanding the events leading up to implantation and to future research on the mechanisms of exchange between the mother and embryo during the initial stages of placentation. This information may be of considerable importance to understanding some of the causes of embryonic loss, which is particularly high around the time of implantation, and to understand some of the basic physiology of the embryo to fill gaps in our knowledge of in vitro fertilization processes. We feel that the mammalian blastocyst provides a unique model for the study of the development of vectorial transport systems in epithelia and, in the future, of patterns of genes that regulate this development.

Amiloride↗