Calcium diffusion in transient and steady states in muscle.

Rates of diffusion through the extracellular space of thin sheets of myocardium from the right ventricular outflow tract of kittens were estimated at 23 degrees C for 45Ca2+ and an inert reference tracer, [14C]sucrose. The myocardial sheets were mounted in an Ussing chamber and equilibrated with Tyrode solution with varied calcium concentrations, Cao. The tracers were added to one side and their concentrations on the other side measured at 5-15-min intervals for 6 h. The apparent tracer diffusion coefficient for sucrose was 1.11 +/- 0.06 X 10(-6) cm2s-1 (mean +/- SEM, n = 74), 22% of the free diffusion coefficient; the lag time before reaching a steady state provided estimates of the intratissue volume of distribution or diffusion space of 0.41 +/- 0.15 ml/ml tissue (n = 74), a value compatible with expectations for extracellular fluid space. Over the range of Cao from 0.02 to 9.0 mM, the intratissue apparent diffusion coefficient for Ca, DCa, averaged 1.65 +/- 0.10 X 10(-6) cm2s-1, n = 74, which is 21% of the free DoCa, and was not influenced by Cao. Because transsarcolemmal Ca permeation is slow, DCa is the diffusion coefficient in the extracellular region. The paired ratios DCa/Ds averaged 1.32 +/- 0.05 (n = 67) for all levels of Cao but at physiologic or higher Cao averaged 1.45 +/- 0.07 (n = 39), close to the ratio of free diffusion coefficients, 1.53. Equations distinguishing transient from steady state diffusion were fitted to the data, showing that the apparent distribution volume of "binding sites" external to the diffusion pathway diminished at higher Cao in a fashion suggesting that a least two different Ca2+ binding sites were present.     

Unified description of electrophoresis and diffusion for DNA and other polyions

The electrophoretic mobilities and diffusion coefficients of single- and double-stranded DNA molecules up to 50,000 bases or base pairs in size have been analyzed, using mobilities and diffusion coefficients either measured by capillary electrophoresis or taken from the literature. The Einstein equation suggests that the electrophoretic mobilities (mu) and diffusion coefficients (D) should be related by the expression mu/D = Q/k(B)T, where Q is the charge of the polyion (Q = ze(o), where z is the number of charged residues and e(o) is the fundamental electronic charge), k(B) is Boltzmann's constant, and T is the absolute temperature. If this equation were true, the ratio mu/zD should be a constant equal to e(o)/k(B)T (39.6 V(-1)) at 20 degrees C. However, the ratio mu/zD decreases with an increase in molecular weight for both single- and double-stranded DNAs. The mobilities and diffusion coefficients are better described by the modified Einstein equation mu/N(m)D = e(o)/k(B)T, where N is the number of repeat units (bases or base pairs) in the DNA and m is a constant equal to the power law dependence of the diffusion coefficients on molecular weight. The average value of the ratio mu/N(m)D is 40 +/- 4 V(-1) for 36 single- and double-stranded DNA molecules of different sizes, close to the theoretically expected value. The generality of the modified Einstein equation is demonstrated by analyzing literature values for sodium polystyrenesulfonate (PSS). The average value of the ratio mu/N(m)D is 35 +/- 6 V(-1) for 14 PSS samples containing up to 855 monomers.     

Tissue oxygen extraction during hypovolemia: role of hemoglobin P50

When the delivery of O2 to tissues (QO2 = blood flow X O2 content) falls below a critical threshold, tissue O2 uptake (VO2) becomes limited by QO2. The mechanism responsible for this extraction limitation is not understood but may involve molecular diffusion limitation as mean capillary PO2 drops below a critical minimum level in some capillaries. We tested this hypothesis by measuring the critical QO2 necessary to maintain VO2 independent of QO2 in anesthetized, paralyzed normal dogs (n = 7) and in a second group in which PO2 at 50% saturation of hemoglobin (P50) was reduced by exchange transfusion with low-P50 erythrocytes (n = 7). QO2 was reduced in stages by removing blood volume to reduce blood flow while VO2 was measured by spirometry at each step. To the extent that O2 extraction was limited by a critical capillary PO2, we reasoned that the onset of diffusion limitation should occur at a higher QO2 with low P50, since a lower end-capillary PO2 is required to achieve the same O2 extraction. The critical QO2 (7.8 +/- 1.2 ml X min-1 X kg-1) and extraction ratio (0.63 +/- 0.06) in dogs with reduced P50 were not different from controls. At the critical delivery, mixed venous PO2 was lower in low P50 (16.1 +/- 2.9 Torr) than controls (29.9 +/- 2.3 Torr). We concluded that diffusion limitation does not initiate the early fall in VO2 below the critical QO2 and offer an alternative model to explain the onset of supply dependency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diffusion of water in cat ventricular myocardium

The rates of diffusion of tritiated water (THO) and [14C]sucrose across cat right ventricular myocardium were studied at 23 degrees C in an Ussing-type diffusion cell, recording the time-course of increase in concentration of tracer in one chamber over 4--6 h after adding tracers to the other. Sucrose data were fitted with a model for a homogeneous sheet of uneven thickness in which the tissue is considered to be an array of parallel independent pathways (parallel pathway model) of varying length. The volume of the sucrose diffusion space, presumably a wholly extracellular pathway, was 23% of the tissue or 27.4 +/-1.7% (mean +/- SEM; n=11) of the tissue water. The effective intramyocardial sucrose diffusion coefficient, D8, was 1.51 +/- 0.19 X 10(-6)cm2.s-1 (n=11). Combining these data with earlier data, D8 was 22.6 +/- 1.1% (n=95) of the free diffusion coefficient in aqueous solution D degrees 8. The parallel pathway model and a dead-end pore model, which might have accounted for intracellular sequestration of water, gave estimates of DW/D degrees W (observed/free) of 15%. Because hindrance to water diffusion must be less than for sucrose (where D8/D degrees 8=22.6%), this showed the inadequacy of these models to account simultaneously for the diffusional resistance and the tissue water content. The third or cell-matrix model, a heterogeneous system of permeable cells arrayed in the extracellular matrix, allowed logical and geometrically reasonable interpretations of the steady-state data and implied estimates of DW in the cellular and extracellular fluid of approximately 25% of the aqueous diffusion coefficient.     

Cytoplasmic hydrogen ion diffusion coefficient.

The apparent cytoplasmic proton diffusion coefficient was measured using pH electrodes and samples of cytoplasm extracted from the giant neuron of a marine invertebrate. By suddenly changing the pH at one surface of the sample and recording the relaxation of pH within the sample, an apparent diffusion coefficient of 1.4 +/- 0.5 x 10(-6) cm2/s (N = 7) was measured in the acidic or neutral range of pH (6.0-7.2). This value is approximately 5x lower than the diffusion coefficient of the mobile pH buffers (approximately 8 x 10(-6) cm2/s) and approximately 68x lower than the diffusion coefficient of the hydronium ion (93 x 10(-6) cm2/s). A mobile pH buffer (approximately 15% of the buffering power) and an immobile buffer (approximately 85% of the buffering power) could quantitatively account for the results at acidic or neutral pH. At alkaline pH (8.2-8.6), the apparent proton diffusion coefficient increased to 4.1 +/- 0.8 x 10(-6) cm2/s (N = 7). This larger diffusion coefficient at alkaline pH could be explained quantitatively by the enhanced buffering power of the mobile amino acids. Under the conditions of these experiments, it is unlikely that hydroxide movement influences the apparent hydrogen ion diffusion coefficient.     

Physical and kinetic properties of homogenous bovine lens aldose reductase.

Aldose reductase from calf lens was purified 15,000-fold. The homogeneity of the final preparation was demonstrated by molecular sieve chromatography, analytical ultracentrifugation, sodium dodecyl sulfate gel electrophoresis, Ouchterlony immunodiffusion, and polyacrylamide gel electrophoresis at three pH values. The monomeric nature of the enzyme is suggested by the molecular weight of 37,000 from both molecular sieve chromatography and sodium dodecyl sulfate-gel electrophoresis with beta-mercaptoethanol. This closely corresponds with a molecular weight of 40,400 estimated by using calculate physical constants in the Svedberg equation. The S20,w was 3.6 to 3.7 as determined from ultracentrifuge and sucrose density gradient data. The Stokes radius was found to be 2.5 +/- 0.2 nm and 2.75 +/- 0.15 nm by two different methods. The diffusion constant D20,w is (7.8 +/- 10(-7) +/- 0.45 X 10(-7) cm2/s). The molecule is nearly spherical as indicated by a frictional ratio f/fo = 1.14. The alpha-helical content was estimated from circular dichroism data to be 5% and did not change in the presence of added substrates, products, and some enzyme inhibitors. Homotropic cooperative effects were observed as shown by the concave downward curvature of the reciprocal plots.     

Density distribution of guinea pig myenteric plexus nerve endings containing immunoreactive substance P

The present study was performed to investigate how myenteric plexus nerve endings containing substance P are distributed in sucrose density gradients in relation to nerve endings capable of taking up 3H-acetylcholine or 14C-noradrenaline. The peak of substance P-immunoreactivity (ISP) was found at a density of 1.157 +/- 0.001 g X ml-1, that of 3H-radioactivity at 1.160 +/- 0.002 and that of 14C-radioactivity at 1.162 +/- 0.002 g X ml-1 (mean +/- SEM, N = 6); there was considerable overlap. In a second set of experiments, the resuspended P2-pellet was layered upon a discontinuous density gradient consisting of 0.6, 1.0, 1.2 and 1.4 M sucrose. Nine fractions were recovered. There was a 2.5-3.4-fold increase in the relative specific activity of ISP in the 1.2 M fraction (density = 1.154 g X ml-1) and the adjoining interfaces. Conventional electron microscopy showed that synaptosomal elements were present in the transmitter-enriched fractions. It is concluded that the substance P-containing nerve endings of the guinea pig myenteric plexus co-distribute (and may be co-purified with) nerve endings utilizing noradrenaline or acetylcholine on sucrose density gradients.     

Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears

The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 +/- 12 compared with 402 +/- 14 g; P = 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 +/- 14 compared with 143.2 +/- 20 ms; P = 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 +/- 0.07 in the active bears and decreased to 0.42 +/- 0.03 (P = 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly bears.     

Kinetic comparison of free weight and machine power cleans

The purpose of this investigation was to compare the kinetic characteristics of the power clean exercise using either free weight or machine resistance. After familiarization, 14 resistance trained men (mean +/- SD; age = 24.9 +/- 6.2 years) participated in two testing sessions. During the initial testing session, one-repetition maximum performance (1RM) was assessed in either the free weight or machine power clean from the midthigh. This was followed by kinetic assessment of either the free weight or the machine power clean at 85% of 1RM. One week after the initial testing session, 1RM performance, as well as the subsequent kinetic evaluation, were performed for the alternate exercise modality. All performance measures were obtained using a computer-interfaced FiTROdyne dynamometer (Fitronic; Bratislava, Slovakia). Maximum strength (1RM) and average power were significantly greater for the free weight condition, whereas peak velocity and average velocity were greater for the machine condition (p < 0.05). Although peak power was not different between modalities, force at peak power (free weights = 1445 +/- 266 N, machine = 1231 +/- 194 N) and velocity at peak power (free weights = 1.77 +/- 0.28 m x s(-1), machine = 2.20 +/- 0.24 m x s(-1)) were different (p < 0.05). It seems that mechanical limitations of the machine modality (i.e., lift trajectory) result in different load capacities that produce different kinetic characteristics for these two lifting modalities.     

Effects of mammary engorgement and feed withdrawal on microvascular function in lactating goat mammary glands

The responses of the mammary microvasculature in lactating goats (n = 8) during feed withdrawal (18-20 h) and mammary engorgement (26-28 h of milk accumulation) were compared using an indicator-dilution technique with FITC-albumin and [(14)C]sucrose as the intravascular and diffusible indicators, respectively. Feed withdrawal and mammary engorgement caused a 50-60% decrease in mammary arterial flow and in the permeability-surface area product (PS) values for sucrose. Only feed withdrawal increased the mean transit time [from 17.3 to 30.0 s, SE of the difference (SED) = 2.16, P < 0.01] of FITC-albumin, whereas only mammary engorgement reduced sucrose extraction (0.63 to 0.51, SED = 0.04, P < 0.05). Mammary engorgement also caused a substantial reduction in the sucrose-accessible extravascular space from 92 to 44 ml (SED = 15.2, P < 0.01). In a separate experiment using five goats, milking after mammary engorgement did not immediately restore arterial flow or sucrose extraction, indicating that the effect of milk accumulation was not mediated simply via increased intramammary pressure. In conclusion, feed withdrawal resulted in slower flow in the capillary bed but apparently no change in capillary recruitment, whereas mammary engorgement caused capillary derecruitment.     

Selective permeability of the blood-uterine lumen barrier in rats: importance of molecular size

To investigate the influence of molecular size on the abilities of polar, nonelectrolytic substances to diffuse passively across the blood-uterine lumen barrier, the abilities of [3H] mannitol, [3H] sucrose and [3H] inulin (mol. wt. 182, 342 and 5200, respectively) to enter uterine luminal fluid from blood were compared in immature, ovariectomized rats implanted for 3 days with Silastic capsules containing estradiol. Relatively constant serum radioactivity concentrations were achieved for the period of 1-4 h after intravenous injection of the test substances by tightly ligating the renal pedicles of all animals prior to injection. Although uterine fluid radioactivity concentrations for [3H] inulin increased significantly between 1 and 4 h after injection, those for [3H] sucrose and [3H] mannitol did not change significantly with time, thus preventing calculation of conventional permeability indices. Therefore, the ratios of uterine fluid to serum radioactivity concentrations 2 h after intravenous injection of the test substances into animals with ligated renal pedicles were determined; the ratios (means +/- SEM) for [3H] mannitol, [3H] sucrose and [3H]-inulin were 0.11 +/- 0.015, 0.038 +/- 0.011 and 0.037 +/- 0.012, respectively. As indicated by these ratios, the rate of transfer into the uterine lumen of [3H] mannitol relative to that of [3H] sucrose was markedly greater than predicted by the ratio of their respective aqueous diffusion coefficients at body temperature. This disproportionality suggested that diffusion across the blood-uterine lumen barrier by some substances is governed by molecular sieving (sterically restricted diffusion) and therefore that this barrier is selectively permeable to these substances on the basis of molecular size.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biosynthesis of intestinal microvillar proteins. The intracellular transport of aminopeptidase N and sucrase-isomaltase occurs at different rates pre-Golgi but at the same rate post-Golgi

The kinetics of processing and microvillar expression of aminopeptidase N (EC 3.4.11.2) and sucrose alpha-D-glucohydrolase-oligo-1,6-glucosidase (sucrase-isomaltase, EC 3.2.1.48 and EC 3.2.1.10) were compared by labelling of pig small intestinal mucosal explants with [35S]methionine. The conversion from transient (high mannose glycosylated) to mature (complex glycosylated) form was 1.7-times slower for sucrase-isomaltase than for aminopeptidase N, indicating a slower rate of migration from the rough endoplasmic reticulum to the Golgi complex. Likewise, sucrase-isomaltase appeared in the microvillar fraction at a slower rate than aminopeptidase N. The relative pool sizes of mature and transient forms of both enzymes in intracellular membranes (Mg2+-precipitated fraction) were determined to obtain information on the relative time, spent pre- and post-Golgi, respectively, prior to microvillar expression. This ratio was 0.24 +/- 0.06 (mean +/- SD) for sucrase-isomaltase as compared to 0.40 +/- 0.04 (mean +/- SD) for aminopeptidase N. Considering the slower rate of pre-Golgi transport for sucrase-isomaltase, this indicates that the two microvillar enzymes have rather similar if not identical rates of post-Golgi transport.     

Hindlimb unweighting alters endothelium-dependent vasodilation and ecNOS expression in soleus arterioles.

The purpose of this study was to test the hypothesis that endothelium-dependent dilation is impaired in soleus resistance arteries from hindlimb-unweighted (HLU) rats. Male Sprague-Dawley rats (300-350 g) were exposed to HLU (n = 14) or weight-bearing control (Con, n = 14) conditions for 14 days. After the 14-day treatment period, soleus first-order (1A) arterioles were isolated and cannulated with micropipettes to assess vasodilator responses to an endothelium-dependent dilator, ACh (10(-9)-10(-4) M), and an endothelium-independent dilator, sodium nitroprusside (SNP, 10(-9)-10(-4) M). Arterioles from HLU rats were smaller than Con arterioles (maximal passive diameter = 140 +/- 4 and 121 +/- 4 microm in Con and HLU, respectively) but developed similar spontaneous myogenic tone (43 +/- 3 and 45 +/- 3% in Con and HLU, respectively). Arteries from Con and HLU rats dilated in response to increasing doses of ACh, but dilation was impaired in arterioles from HLU rats (P = 0.03), as was maximal dilation to ACh (85 +/- 4 and 65 +/- 4% possible dilation in Con and HLU, respectively). Inhibition of nitric oxide (NO) synthase (NOS) with N(omega)-nitro-L-arginine (300 microM) reduced ACh dilation by approximately 40% in arterioles from Con rats and eliminated dilation in arterioles from HLU rats. The cyclooxygenase inhibitor indomethacin (50 microM) did not significantly alter dilation to ACh in either group. Treatment with N(omega)-nitro-L-arginine + indomethacin eliminated all ACh dilation in Con and HLU rats. Dilation to sodium nitroprusside was not different between groups (P = 0.98). To determine whether HLU decreased expression of endothelial cell NOS (ecNOS), mRNA and protein levels were measured in single arterioles with RT-PCR and immunoblot analysis. The ecNOS mRNA and protein expression was significantly lower in arterioles from HLU rats than in Con arterioles (20 and 65%, respectively). Collectively, these data indicate that HLU impairs ACh dilation in soleus 1A arterioles, in part because of alterations in the NO pathway.     

Pulmonary diffusing capacity for nitric oxide during exercise in morbid obesity

Morbidly obese individuals may have altered pulmonary diffusion during exercise. The purpose of this study was to examine pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) during exercise in these subjects. Ten morbidly obese subjects (age = 38 +/- 9 years, BMI = 47 +/- 7 kg/m(2), peak oxygen consumption or VO(2peak) = 2.4 +/- 0.4 l/min) and nine nonobese controls (age = 41 +/- 9 years, BMI = 23 +/- 2 kg/m(2), VO(2peak) = 2.6 +/- 0.9 l/min) participated in two sessions: the first measured resting O(2) and VO(2peak) for determination of wattage equating to 40, 75, and 90% oxygen uptake reserve (VO(2)R). The second session measured pulmonary diffusion from single-breath maneuvers of 5 s each, as well as heart rate (HR) and VO(2) over three workloads. DLNO, DLCO, and pulmonary capillary blood volume were larger in obese compared to nonobese groups (P 0.10). The morbidly obese have increased pulmonary diffusion per unit increase in VA compared with nonobese controls which may be due to a lower rise in VA per unit increase in VO(2) in the obese during exercise.     

Bone strontium in pregnant and lactating females from archaeological samples

Because plants and animals consume or absorb different amounts of strontium and calcium, anthropologists are able to use strontium/calcium (Sr/Ca) ratios from archaeologically recovered human bone to estimate the relative contributions of meat and plants to paleodiets. Often females exhibit higher Sr/Ca ratios than males, a fact usually attributed to lower meat intake among women. However, in vivo and in vitro experiments with laboratory animals show that pregnancy and lactation elevate maternal bone strontium and depress maternal bone calcium because 1) strontium is discriminated against in favor of calcium in the transport of ions to the placenta and mammary glands and 2) pregnancy and lactation facilitate absorption of alkaline earth metals from the gut. In this study, bone Sr/Ca ratios and strontium concentrations were compared between reproductive-age females, postmenopausal females, and adult males from two late prehistoric Native American sites in Georgia: the King site (N = 43) and the Etowah site (N = 51). At the King site, the mean Sr/Ca ratio of females was over 14% greater than that of males. At Etowah, the mean strontium level of reproductive-age females exceeded that of postmenopausal females by almost 25%. Most of the difference, it is argued, is due to pregnancy and lactation. A dietary preference among pregnant and lactating women for foods high in alkaline earths, particularly nuts and corn, may also be partially responsible. Until we assess the influence variables other than nutrition exert on trace element concentrations, our reconstructions of paleodiets will be suspect.     

Regulation of bovine brain microvascular endothelial tight junction assembly and barrier function by laminar shear stress

Blood-brain barrier (BBB) controls paracellular solute diffusion into the brain microenvironment and is maintained primarily by tight junctions between adjacent microvascular endothelial cells. Studies implicate blood flow-associated shear stress as a pathophysiological mediator of BBB function, although detailed biochemical data are scarce. We hypothesize that shear stress upregulates BBB function via direct modulation of expression and properties of pivotal tight-junction proteins occludin and zonula occludens-1 (ZO-1). Bovine brain microvascular endothelial cells (BBMvECs) were exposed to either steady or pulsatile shear stress (10 and 14 dyn/cm(2), respectively) for 24 h. Sheared BBMvECs were monitored for occludin-ZO-1 expression, association, and subcellular localization, and transendothelial permeability of BBMvECs to FITC-dextran and (14)[C]sucrose was assessed. Actin reorganization and BBMvEC realignment were observed following steady shear stress for 24 h. Substantial increases in occludin mRNA and protein expression (2.73 +/- 0.26- and 1.83 +/- 0.03-fold) and in occludin-ZO-1 association (2.12 +/- 0.15-fold) were also observed. Steady shear stress also induced clear relocalization of both proteins to the cell-cell border in parallel with reduced transendothelial permeability to FITC-dextran (but not sucrose). Following pulsatile shear stress, increased protein levels for both occludin and ZO-1 (2.15 +/- 0.02- and 1.67 +/- 0.21-fold) and increased occludin-ZO-1 association (2.91 +/- 0.14-fold) were observed in parallel with a reduction in transendothelial permeability to (14)[C]sucrose. Shear stress upregulates BBMvEC barrier function at the molecular level via modulation of expression, association, and localization of occludin and ZO-1. The pulsatile shear model appeared to give the most profound biochemical responses.     

Slow diffusion of K+ in the T tubules of rat cardiomyocytes.

Cardiomyocyte contractility is regulated by the extracellular K(+) concentration ([K(+)](o)). Potassium dynamics in the T tubules during the excitation-contraction cycle depends on the diffusion rate of K(+), but this rate is not known. Detubulation of rat cardiomyocytes was induced by osmotic shock using formamide, which separated the surface membrane from the T tubules. Changes in current and membrane potential in voltage-clamped (-80 mV) and current-clamped control and detubulated cardiomyocytes were compared during rapid switches between 5.4 and 8.1 mM [K(+)](o), and the results were simulated in a mathematical model. In the voltage-clamp experiments, the current changed significantly slower in control than in detubulated cardiomyocytes during the switch from 5.4 to 8.1 mM [K(+)](o), as indicated by the times to achieve 25, 50, 90, and 95% of the new steady-state current [control (ms) t(25) = 98 +/- 12, t(50) = 206 +/- 20, t(90) = 570 +/- 72, t(95) = 666 +/- 92; detubulated t(25) = 61 +/- 11, t(50) = 142 +/- 17, t(90) = 352 +/- 52, t(95) = 420 +/- 69]. These time points were not significantly different either during the 8.1 to 5.4 mM [K(+)](o) switch or in current-clamped cardiomyocytes switching from 5.4 to 8.1 mM [K(+)](o). Mathematical simulation of the difference current between control and detubulated cardiomyocytes gave a t-tubular diffusion rate for K(+) of approximately 85 mum(2)/s. We conclude that the diffusion of K(+) in the T tubules is so slow that they constitute a functional compartment. This might play a key role in local regulation of the action potential, and thus in the regulation of cardiomyocyte contractility.     

Human lung density is not altered following normoxic and hypoxic moderate-intensity exercise: implications for transient edema.

The purpose of this study was to examine the effects of exercise on extravascular lung water as it may relate to pulmonary gas exchange. Ten male humans underwent measures of maximal oxygen uptake (Vo2 max) in two conditions: normoxia (N) and normobaric hypoxia of 15% O2 (H). Lung density was measured by quantified MRI before and 48.0 +/- 7.4 and 100.7 +/- 15.1 min following 60 min of cycling exercise in N (intensity = 61.6 +/- 9.5% Vo2 max) and 55.5 +/- 9.8 and 104.3 +/- 9.1 min following 60 min cycling exercise in H (intensity = 65.4 +/- 7.1% hypoxic Vo2 max), where Vo2 max = 65.0 +/- 7.5 ml x kg(-1) x min(-1) (N) and 54.1 +/- 7.0 ml x kg(-1) x min(-1) (H). Two subjects demonstrated mild exercise-induced arterial hypoxemia (EIAH) [minimum arterial oxygen saturation (SaO2 min) = 94.5% and 93.8%], and seven subjects demonstrated moderate EIAH (SaO2 min = 91.4 +/- 1.1%) as measured noninvasively during the Vo2 max test in N. Mean lung densities, measured once preexercise and twice postexercise, were 0.177 +/- 0.019, 0.181 +/- 0.019, and 0.173 +/- 0.019 g/ml (N) and 0.178 +/- 0.021, 0.174 +/- 0.022, and 0.176 +/- 0.019 g/ml (H), respectively. No significant differences (P > 0.05) were found in lung density following exercise in either condition or between conditions. Transient interstitial pulmonary edema did not occur following sustained steady-state cycling exercise in N or H, indicating that transient edema does not result from pulmonary capillary leakage during sustained submaximal exercise.