PubMed Health⌕ Search

Biomedical subjects

F E Curry

Publications and source records attributed to F E Curry.

At least 19 recordsLinked to original sources
PubMed2000

Dominant role of cAMP in regulation of microvessel permeability.

We reported previously that increasing cAMP levels in endothelial cells attenuated ATP-induced increases in hydraulic conductivity (L(p)), and that the activation of cGMP-dependent pathways was a necessary step to increase L(p) in response to inflammatory mediators. The aim of the present study was to evaluate the role of basal levels of cAMP in microvessel permeability under resting conditions and to evaluate the cross talk between cAMP- and cGMP-dependent signaling mechanisms in regulation of microvessel permeability under stimulated conditions, using individually perfused microvessels from frog and rat mesenteries. We found that reducing cAMP levels by inhibition of adenylate cyclase or inhibiting cAMP-dependent protein kinase through the use of H-89 increased basal L(p) in both frog and rat mesenteric venular microvessels. We also found that 8-bromocAMP (8-BrcAMP, 0.2 and 2 mM) was sufficient to attenuate or abolish the increases in L(p) due to exposure of frog mesenteric venular microvessels to 8-BrcGMP (2 mM) and ATP (10 microM). Similarly, in rat mesenteric venular microvessels, application of 8-BrcAMP (2 mM) abolished the increases in L(p) due to exposure to 8-BrcGMP alone (2 mM) or with the combination of bradykinin (1 nM). In addition, application of erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of cGMP-stimulated phosphodiesterase, significantly attenuated both 8-BrcGMP- and bradykinin-induced increases in L(p). These results demonstrate that basal levels of cAMP are critical to maintaining normal permeability under resting conditions, and that increased levels of cAMP are capable of overcoming the activation of cGMP-dependent pathways, therefore preventing increases in microvessel permeability. The balance between endothelial concentrations of these two opposing cyclic nucleotides controls microvessel permeability, and cAMP levels play a dominant role.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Endothelial cell shrinkage increases permeability through a Ca2+-dependent pathway in single frog mesenteric microvessels.

1. We tested whether calcium (Ca2+)-dependent mechanisms were essential for our previous observation that a change in the endothelial cell (EC)-extracellular matrix (ECM) attachment caused an increase in microvessel hydraulic permeability (Lp) after exposure to hypertonic solutions in single perfused mesenteric microvessels in pithed frogs (Rana pipiens). 2. In microvessels where integrin-dependent EC-ECM attachments were disrupted by pretreatment with the peptide Gly-Arg-Gly-Asp-Thr-Pro (GRGDTP; 0.3 mmol l-1), we measured microvessel Lp after exposure to hypertonic solutions under experimental conditions that reduced Ca2+ influx into endothelial cells. 3. High K+ solutions (59.7 and 100 mmol l-1 K+) were used to depolarize the endothelial membrane and therefore to reduce the electrochemical driving force for Ca2+ influx through conductive Ca2+ channels. These solutions abolished the increase in Lp caused by hypertonic solutions in the microvessels pretreated with GRGDTP. 4. We previously suggested that the removal of albumin from the perfusate may reduce EC-ECM attachment because hypertonic solutions increased the Lp of microvessels above that due to removal of albumin alone. This additional increase in Lp was attenuated by the 59.7 mmol l-1 K+ solution and was completely abolished by the 100 mmol l-1 K+ solution. 5. Bumetanide, an inhibitor of the Na+-K+-2Cl- co-transporter and one of the mechanisms of regulatory volume increase after exposure to hypertonic solutions in endothelial cells, did not change the response of microvessels to high K+ solutions. 6. Our findings indicate that Ca2+ entry into endothelial cells via passive conductance channels is necessary to increase microvessel Lp after exposure to hypertonic solutions in microvessels where EC-ECM attachments are disrupted.

Albumins↗
PubMed1999

Microvascular permeability.

This review addresses classical questions concerning microvascular permeabiltiy in the light of recent experimental work on intact microvascular beds, single perfused microvessels, and endothelial cell cultures. Analyses, based on ultrastructural data from serial sections of the clefts between the endothelial cells of microvessels with continuous walls, conform to the hypothesis that different permeabilities to water and small hydrophilic solutes in microvessels of different tissues can be accounted for by tortuous three-dimensional pathways that pass through breaks in the junctional strands. A fiber matrix ultrafilter at the luminal entrance to the clefts is essential if microvascular walls are to retain their low permeability to macromolecules. Quantitative estimates of exchange through the channels in the endothelial cell membranes suggest that these contribute little to the permeability of most but not all microvessels. The arguments against the convective transport of macromolecules through porous pathways and for the passage of macromolecules by transcytosis via mechanisms linked to the integrity of endothelial vesicles are evaluated. Finally, intracellular signaling mechanisms implicated in transient increases in venular microvessel permeability such as occur in acute inflammation are reviewed in relation to studies of the molecular mechanisms involved in signal transduction in cultured endothelial cells.

Animals↗
PubMed1998

cGMP modulates basal and activated microvessel permeability independently of [Ca2+]i.

To investigate the mechanisms whereby guanosine 3',5'-cyclic monophosphate (cGMP) modulates microvessel permeability in vivo, we measured changes in microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic Ca2+ concentration ([Ca2+]i) in response to the cGMP analogs 8-bromo-cGMP (8-BrcGMP) and 8-(p-chlorophenylthio)cGMP (8-pCPT-cGMP) in the presence and absence of inflammatory stimuli in intact individually perfused microvessels in frog and rat mesenteries. The cGMP analog caused a transient increase in Lp and potentiated ATP or bradykinin-induced increases in Lp in frog and rat mesenteric microvessels, respectively. The mean peak value of the test Lp/control Lp after exposure to 8-BrcGMP was 5.3 +/- 0.5 in frog microvessels and 2.8 +/- 0.4 in rat microvessels. The ATP-induced increase in Lp in frog microvessels was further raised by 8-BrcGMP from 7.0 +/- 0.9 to 12.4 +/- 1.9 times the control. In rat mesenteric microvessels, the bradykinin-induced increase in Lp was potentiated by 8-BrcGMP from 4.8 +/- 0.4 to 8.3 +/- 1.3 times the control and was suppressed by the guanylate cyclase inhibitor LY-83583 to 2.6 +/- 0.5 times the control. A similar but larger effect was found when using 8-pCPT-cGMP. In contrast to the actions of increased cGMP on microvessel permeability, cGMP analogs had no effect on basal endothelial [Ca2+]i and did not alter the magnitude and time course of ATP or bradykinin-induced increases in endothelial [Ca2+]i. These results suggested that an elevation of cGMP levels in endothelial cells is a necessary step to increase microvessel permeability in intact microvessels, and this regulatory process occurs downstream from Ca2+ influx, which differs from that reported in large-vessel endothelium in culture and in vascular smooth muscle cells. Experiments carried on microvessels in both frog and rat mesenteries provided a direct comparison of the endothelial cell regulatory mechanisms between species.

Adenosine Triphosphate↗
PubMed1998

Microvascular permeability and number of tight junctions are modulated by cAMP.

We tested the hypothesis that increased endothelial cell adenosine 3',5'-cyclic monophosphate (cAMP) decreases microvascular permeability in vivo. The effects of cAMP-specific phosphodiesterase type IV inhibition and adenylate cyclase activation on microvascular hydraulic conductivity (Lp) were investigated in intact individual capillaries and postcapillary venules in mesentery of pithed frogs (Rana pipiens). Treatment with rolipram (10 microM) and forskolin (5 microM) for 25 min decreased Lp to 37% of control. Rolipram alone also significantly decreased Lp. Isoproterenol (10 microM) decreased Lp to 27% of control within 20 min. A subgroup of eight vessels treated with rolipram and forskolin, in which mean Lp fell to 25% of control, was examined with transmission electron microscopy. The mean number of tight junctions in the treated vessels was 2.2 per cleft (303 clefts), significantly higher than in a matched control group (192 clefts), which was 1.7 per cleft. The results indicate that microvascular Lp can be modulated by intracellular cAMP and that one of the structural end points of stimulated cAMP levels is an increase in the mean number of tight-junction strands between endothelial cells.

Adrenergic beta-Agonists↗
PubMed1998

Test of a two-pathway model for small-solute exchange across the capillary wall.

We previously proposed a two-pathway model for solute and water transport across vascular endothelium (Fu, B. M., R. Tsay, F. E. Curry, and S. Weinbaum. J. Biomech. Eng. 116: 502-513, 1994) that hypothesized the existence of a continuous slit 2 nm wide along tight junction strands within the interendothelial cleft in parallel with 20 x 150-nm breaks in tight junctions. We tested this model by measuring capillary permeability coefficients (P) to a small solute (sodium fluorescein, radius 0.45 nm), assumed to permeate primarily the 2-nm small pore, and an intermediate-sized solute (FITC-alpha-lactalbumin, radius 2.01 nm) excluded from the small pore. Mean values of the paired diffusive permeability coefficients, Psodium fluorescein and PFITC-alpha-lactalbumin, were 34.4 and 2.9 x 10(-6) cm/s, respectively, after corrections for solvent drag and free dye (n = 26). These permeabilities were accounted for by transport through the large-break pathway without the additional capacity of the hypothetical 2-nm pathway. As a further test we examined the relative reductions of Psodium fluorescein and PFITC-alpha-lactalbumin produced by elevated intracellular cAMP. Within 20 min after the introduction of rolipram and forskolin, Psodium fluorescein and PFITC-alpha-lactalbumin decreased to 0.67 and 0.64 times their respective baseline values. These similar responses to permeability decrease were evidence that the two solutes were carried by a common pathway. Combined results in both control and reduced permeability states did not support the hypothesis that a separate pathway across tight junctions is available for solutes with a radius as large as 0.75 nm. If such a pathway is present, then its size must be smaller than that of sodium fluorescein.

Animals↗
PubMed1997

Effect of cell shrinkage on permeability of cultured bovine aortic endothelia and frog mesenteric capillaries.

1. We have tested the hypothesis that a reduction in endothelial cell volume increases microvessel permeability and that the degree of endothelial cell attachment to their basement membranes determines the magnitude of permeability changes caused by a reduction in endothelial cell volume. 2. A decrease in endothelial cell volume was imposed on both intact microvessels and cultured endothelial monolayers by raising osmolarity by 100 mosmol l-1. 3. We found that hypertonic solutions did not increase the hydraulic permeability (Lp) of individually perfused venular microvessels in frog mesentery when the perfusate contained albumin. Hypertonic solutions did increase Lp, however, after we perfused the microvessels with the peptide Gly-Arg-Gly Asp-Thr-Pro (GRGDTP; 0.3 mmol l-1), to disrupt integrin-dependent endothelial cell (EC) attachment to the extracellular matrix (ECM). 4. After albumin was removed from the perfusate, hypertonic solutions increased Lp of microvessels and the permeability of endothelial monolayers to alpha-lactalbumin. 5. Our findings indicate that endothelial cell integrin-ECM binding plays a role in transducing changes in cell volume and/or shape into changes in permeability. We hypothesize that removal of albumin from the vascular perfusate may compromise EC-ECM interactions via an integrin-dependent mechanism.

Animals↗
PubMed1997

Effect of nitric oxide synthase inhibitors on endothelial [Ca2+]i and microvessel permeability.

To investigate the mechanism whereby nitric oxide (NO) signaling pathways regulate microvessel permeability in vivo, we measured changes in microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic calcium concentration ([Ca2+]i) in response to calcium ionophore, ionomycin (5 microM), and ATP (10 microM) before and after the use of NO synthase (NOS) inhibitors in single perfused frog mesenteric venular microvessels. Ionomycin induced a transient increase in endothelial [Ca2+]i and an associated increase in Lp. The NOS inhibitors N omega-nitro-L-arginine methyl ester (10 and 300 microM) and N omega-monomethyl-L-arginine (L-NMMA; 10, 50, and 100 microM) significantly attenuated the peak increase in Lp induced by ionomycin. A similar inhibitory effect was also observed with the increase in Lp mediated by ATP. In contrast, D-NMMA, a biologically inactive isomer of L-NMMA, showed no effect on ionomycin-induced increase in Lp L-Arginine (3 mM) reversed the inhibitory effect of L-NMMA (10 microM) on Lp. However, the NOS inhibitors did not alter the magnitude and time course of the biphasic increase in endothelial [Ca2+]i induced by both ionomycin and ATP. These data suggest that 1) calcium-dependent NO release is a necessary step to increase microvessel permeability, and 2) the action of NOS inhibitors in attenuating the permeability increase in response to ionomycin and ATP occurs down-stream from calcium entry and does not involve modification of the initial increase in endothelial [Ca2+]i.

Adenosine Triphosphate↗
PubMed1997

Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway.

We tested the hypothesis that vascular endothelial growth factor (VEGF) increases microvascular permeability by increasing calcium influx into endothelial cells forming the vessel walls. We measured microvessel hydraulic conductivity (Lp) in isolated perfused MS-222-anesthetized frog mesenteric microvessels during perfusion with VEGF under conditions that attenuate calcium influx. VEGF increased Lp during a second successive perfusion in the same microvessel by 7.8-fold, which was not significantly different from that brought about by an initial application of VEGF (5.0-fold). However, under depolarizing conditions, the increase in Lp was reduced from 11.1- to 5.6-fold when depolarized to -10 mV (58 mM K+) and to 2.8-fold when depolarized to 0 mV (100 mM K+). Attenuating calcium influx by the addition of nickel ions resulted in a similar attenuation of the increase in Lp (from 13- to 2.5-fold). VEGF also increased the intracellular calcium concentration in endothelial cells of perfused microvessels as determined by measurement with fura 2. We therefore conclude that VEGF increases Lp by increasing calcium influx.

Animals↗
PubMed1997

Effect of nitric oxide synthase inhibitors on basal microvessel permeability and endothelial cell [Ca2+]i.

We evaluated the role of basal nitric oxide (NO) release in the regulation of microvessel permeability under resting conditions. We measured changes in microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic calcium concentration ([Ca2+]i) after application of NO synthase (NOS) inhibitors to the lumen of individually perfused frog mesenteric venular microvessels. NOS inhibitors caused a transient increase in Lp. The mean ratios of peak test Lp values relative to control values in the presence of N omega-nitro-L-arginine methyl ester (L-NAME) at concentrations of 1, 10, and 100 microM were 2.5 +/- 0.6, 2.9 +/- 0.7, and 4.8 +/- 0.4, respectively. N omega-monomethyl-L-arginine (L-NMMA) showed a similar effect and a biologically inactive isomer of L-NMMA, D-NMMA, showed no effect. These results demonstrate that basal levels of NO play a role in modulating microvessel permeability different from that due to NO produced in response to inflammatory agents. In the activated state NOS inhibitors attenuated the increased microvessel permeability in response to ionomycin and ATP [P. He, B. Liu, and F. E. Curry. Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H176-H185, 1997]. The transient increase in basal permeability induced by NOS inhibitors was not accompanied by an increase in endothelial cell [Ca2+]i and did not require the presence of extracellular calcium. Application of ketotifen, a mast cell stabilizer, and an iron-chelating reagent, deferoxamine mesylate, attenuated the transient increase in Lp induced by L-NMMA, suggesting that basal NO may have an important antioxidant role in regulating normal permeability.

Animals↗
PubMed1996

Ca2+ entry through conductive pathway modulates receptor-mediated increase in microvessel permeability.

We investigated the relationship between receptor-mediated increases in cytoplasmic Ca2+ concentration ([Ca2+]i) and increased microvessel permeability. In individually perfused venular microvessels of frog mesentery exposed to 10 microM ATP, [Ca2+]i increased from 59 +/- 7 to 172 +/- 21 nM within 1 min and then fell back toward control values. The corresponding peak increase in the hydraulic conductivity (Lp) of the microvessel wall was 5.7 +/- 0.5-fold relative to control. After removal of extracellular Ca2+, there was no significant increase in Lp, and the initial increase in [Ca2+]i was attenuated but not abolished. Depolarization of the endothelial cell membrane with high-K+ Ringer solution reduced the peak increase in [Ca2+]i to 106 +/- 7 nM and attenuated the increase in Lp 1.8 +/- 0.4-fold. The results conform to the hypothesis that Ca2+ entry into endothelial cells is required for acute increase in venular microvessel permeability by inflammatory agents and that the pathway for Ca2+ entry has the properties of a passive conductance pathway. Similar conclusions were reached in previous experiments in frog microvessels exposed to Ca2+ ionophores and perfusates with no plasma proteins. In venular microvessels of hamster mesentery exposed to ATP and bradykinin, a similar pathway for Ca2+ entry was demonstrated in the present experiments. We did not measure permeability changes in hamster microvessels in this study, but these microvessels respond to histamine and ionophores with a transient increase in permeability to macromolecules similar to that measured in frog microvessels [Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1982-H1991, 1995].

Adenosine↗
PubMed1996

Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvessels.

These experiments report the first direct measurement of microvessel permeability coefficients after exposure to vascular endothelial growth factor (VEGF). The Landis technique was extended to enable measurement of the resistance of the microvessel wall to water flow, hydraulic conductivity (Lp), on the same microvessel in the frog mesentery during the initial exposure to VEGF (acute) and 24 and 72 h after initial exposure (chronic). Control measurements of Lp showed no change either acutely or chronically. Exposure to 1 nM VEGF rapidly and transiently increased microvessel Lp within 30 s (to 7.8-fold greater than baseline values) and returned to control within 2 min. The baseline Lp was fivefold greater after 24 h than the initial baseline as a result of VEGF perfusion and returned to its original value after 72 h. These experiments confirm the hypothesis that VEGF acts both acutely (over a period of a few minutes) and chronically (over a few hours) to increase microvascular permeability.

Animals↗
PubMed1995

Measurement of membrane potential of endothelial cells in single perfused microvessels.

The membrane potential is an important modulator of calcium ion flux into endothelial cells of venular microvessels. We developed a method to measure the membrane potential of endothelial cells forming the walls of individually perfused microvessels under the same experimental conditions as those used to measure cytoplasmic calcium concentration and microvessel permeability. The membrane potential-sensitive fluorescent dye, bis-oxonol (1 microM), was added to the perfusate and the changes in bis-oxonol fluorescence intensity (FI) were calibrated in terms of changes in membrane potential using the cationic ionophore, gramicidin. FI changes an average of 0.625% per millivolt. The resting membrane potential of endothelial cells measured in single perfused microvessels, each calibrated individually, was 51.6 +/- 4.9 mV (n = 9). In the presence of high potassium Ringer's solutions (57.9 and 100 mM, [K+]o), the membrane depolarized 25 +/- 3 and 40 +/- 5 mV, respectively. Conversely, low potassium solutions (0.1 mM [K+]o) hyperpolarized the membrane by 23 +/- 4 mV. The endothelial membrane was also depolarized when the Na-K-ATPase was inhibited with ouabain. This method provides new data to test current hypotheses describing the role of the endothelial cell membrane potential as a modulator of microvessel permeability.

Animals↗
PubMed1995

Solvent drag of LDL across mammalian endothelial barriers with increased permeability.

We investigated the mechanisms of hamster low-density lipoprotein (LDL) transport across the endothelial barrier in individually perfused venular microvessels in hamster mesentery. These experiments are the first to use microperfusion techniques and quantitative fluorescence microscopy to investigate LDL transport across mammalian microvessel endothelium. The apparent permeability coefficient for hamster LDL, PsLDL, rose from 2.7 x 10(-7) cm/s at control to 23.2 x 10(-7) cm/s at the peak of the biphasic increase in microvessel permeability after exposure of the vessels to 100 microM histamine. Close to the peak, PsLDL rose 1.85 x 10(-7) cm/s for every centimeter of H2O increase in hydrostatic pressure. Thus, at a mean pressure of 11.3 cmH2O, 90% of the LDL flux was coupled to transendothelial water flow by a solvent drag mechanism. The corresponding solvent drag reflection coefficient for hamster LDL was estimated to be approximately 0.8. These results are consistent with sieving hamster LDL (effective radius 14.9 nm) through equivalent pores of approximately 22 nm radius. Similar results were found with human LDL (effective radius 13.2 nm) in hamster microvessels. The results provide a bridge between studies of LDL transport across cultured endothelial barriers, where high diffusive permeability coefficients to LDL may obscure the contributions of solvent drag, and studies in whole animals, where the consequences of sieving of LDL at the vessel wall, even in the high permeability state, have not received much attention.

Animals↗
PubMed1995

A diffusion wake model for tracer ultrastructure-permeability studies in microvessels.

We developed a time-dependent diffusion model for analyzing the concentration profiles of low-molecular-weight tracers in the interendothelial clefts of the capillary wall that takes into account the three-dimensional time-dependent filling of the surrounding tissue space. The model provides a connecting link between two methods to investigate transvascular exchange: electron-microscopic experiments to study the time-dependent wake formed by low-molecular-weight tracers (such as lanthanum nitrate) on the tissue side of the junction strand discontinuities in the interendothelial cleft of frog mesentery capillaries (R. H. Adamson and C. C. Michel. J. Physiol. Lond. 466: 303-327, 1993) and confocal-microscopic experiments to measure the spread of low-molecular-weight fluorescent tracers in the tissue space surrounding these microvessels (R. H. Adamson, J. F. Lenz, and F. E. Curry, Microcirculation 1: 251-265, 1994). We show that the interpretation of the presence of tracer as an all-or-none indication of a pathway across the junctional strand is likely to be incorrect for small solutes. Large-pore pathways, in which the local tracer flux densities are high, reach a threshold concentration for detection and are likely to be detected after relatively short perfusion times, whereas distributed small-pore pathways may not be detected until the tissue concentrations surrounding the entire vessel approach threshold concentrations. The analysis using this approach supports the hypothesis advanced by Fu et al. (J. Biomech. Eng. 116: 502-513, 1994) that the principal pathways for water and solutes of < 1.0 nm diameter across the interendothelial cleft may be different and suggests new experiments to test this hypothesis.

Blood Vessels↗
PubMed1995

Modelling the structural pathways for transcapillary exchange.

The ultrastructural pathways and mechanisms whereby endothelial cells and the clefts between the cells modulate capillary permeability to water and solutes have been a central unresolved question in microvessel transport since the early 1950s. Freeze-fracture studies and ultrathin serial sections have demonstrated that endothelial cells are joined by an array of junctional strands which are interrupted at intervals, allowing for the passage of water and solutes, whereas cytochemical studies have indicated that the endothelial surface and portions of the wide part of the cleft contain matrix components. Neither constricted slit models based on the classic pore theory nor fiber matrix models are able to explain the large body of existing permeability measurements. In this review, we shall describe new three-dimensional modelling approaches which have resulted in a major revision of current ideas about the pathways for water and solutes through the junction strand and the structures that determine the molecular filter. For frog mesentery capillaries, these models predict (i) that the primary pathway for small ions is a previously unrecognized family of 2nm small pores that are distributed along the length of the junction strand; (ii) that the primary pathway for water and intermediate-sized solutes (1-3.5 nm radius) is an infrequent 150 nm long orifice-like pore whose height is the same as that of the wide part of the cleft; (iii) that the sieving structure for these solutes is a fiber layer, typically 100 nm thick, which extends from the surface into the entrance region of the cleft and (i.v.) that the interpretation of low molecular weight tracer studies to define the permeability pathways depends on the time-dependent filling of the extravascular space.

Animals↗
PubMed1994

A junction-orifice-fiber entrance layer model for capillary permeability: application to frog mesenteric capillaries.

The recent serial section electron microscopic studies by Adamson and Michel (1993) on microves gels of frog mesentery have revealed that the large pores in the junction strand of the interendothelial cleft are widely separated 150 nm wide orifice-like breaks whose gap height 20 nm is the same as the wide part of the cleft. In this paper a modified version of the model in Weinbaum et al. (1992) is first developed in which this orifice structure is explored in combination with a random or ordered fiber matrix layer that is at the luminal surface and/or occupies a fraction of the wide part of the cleft. This basic orifice model predicts that for the measured Lp to be achieved the fiber layer must be confined to a relatively narrow region at the entrance to the cleft where it serves as the primary molecular filter. The model provides a much better fit of the permeability P for intermediate size solutes between 1 and 2 nm radius than the previous model in Weinbaum et al., where the junction strand breaks were treated as finite depth circular or rectangular pores, but like the previous model significantly underestimates P for small ions. However, it is shown that if a small frequent pore of 1.5 nm radius with characteristic spacing comparable to the diameter of the junction proteins or a continuous narrow slit of approximately 1.5 to 2.3 nm gap height is also present in the continuous part of the junction strand, small ion permeability can also be satisfied. The 1.5 nm radius pore does not significantly change Lp, whereas the continuous narrow slit provides a contribution to Lp that is comparable to, or in the case of the 2.3 nm slit greater than, the widely spaced 150 nm orifices. Thus, for the narrow slit the contribution to Lp from the orifices can be as low as 1.0 x 10(-7) cm/s/cm H2O and it is also possible to satisfy the 2.5 fold increase in permeability that occurs when the matrix is enzymatically removed from the luminal side of the cleft, Adamson (1990). The likelihood of each of these cleft structures is discussed.

Animals↗