Ionic transport mechanisms underlying fluid secretion by the pancreas

1981 ◽  
Vol 296 (1080) ◽  
pp. 167-178 ◽  
Keyword(s):  
Carbonic Acid ◽  
Basolateral Membrane ◽  
Extracellular Fluid ◽  
Fluid Secretion ◽  
Bicarbonate Concentration ◽  
Cellular Mechanisms ◽  
Luminal Membrane ◽  
Sodium Gradient ◽  
Characteristic Features ◽  
Sodium And Potassium

The pancreas is a ‘leaky’ epithelium and secretes a juice in which sodium and potassium have concentrations similar to those of plasma. The characteristic features of the secretion are its isosmolality and its high bicarbonate concentration. It is the latter that has attracted considerable attention. Secretion in the isolated cat pancreas is directly proportional to the bicarbonate concentration in the nutrient fluid. The ability of the gland to secrete weak acids has led to the view that because of the very different chemical nature of the anions, it is most likely that it is a component common to all buffers, the proton, that is subject to active transport. This is supported by the decrease in pH and the increase in p co 2 of the venous effluent when secretion occurs and the sensitivity of secretion to the pH of the nutritional extracellular fluid. It is proposed that the cellular mechanisms are as follows: CO 2 diffuses into the cell and is hydrated to carbonic acid under the influence of carbonic anhydrase. The bicarbonate ion so formed diffuses into the ductular lumen and the proton is transported backwards through the epithelium with a proton pump (Mg 2+ -ATPase) provisionally located in the luminal membrane and a hydrogen-sodium exchange carrier located in the basolateral membrane. Energy for the latter process is derived from the sodium gradient between extracellular fluid and cell. This gradient is maintained by a (Na + +K + )-ATPase also located in the basolateral membrane. Chloride appears to be transported partly through a chloride-bicarbonate exchange mechanism, but largely passively together with a large sodium and potassium com ponent through the paracellular pathway. Osmotic equilibrium is likely to occur in the small ductules.

Regulation of electrolyte and fluid secretion in salivary acinar cells

1992 ◽  
Vol 263 (6) ◽  
pp. G823-G837 ◽  
Author(s):  
B. Nauntofte
Keyword(s):  
Ionic Composition ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Receptor Activation ◽  
Exchange Mechanism ◽  
Luminal Membrane ◽  
Net Uptake ◽  
Cl Channels ◽  
Simultaneous Activation

The primary secretion from exocrine gland cells is a fluid rich in Na+ and Cl- with a plasmalike ionic composition. Activation of specific receptors on the plasma membrane by hormones and neurotransmitters, which leads to activation of the phosphoinositol metabolism, results in release of Ca2+ from internal Ca2+ stores. Intracellular free Ca2+ concentration ([Ca2+]i) then rises simultaneously at both the basolateral and luminal parts of the acinar cell, reaching maximum values within 1 s after stimulation. In parotid acinar cells, increased [Ca2+]i activates the opening of maxi K+ channels located on the basolateral membrane and Cl- channels presumably located on the luminal membrane, resulting in rapid loss of K+ and Cl- and water and cell shrinkage. Extracellular electroneutrality is maintained by a paracellular Na+ flux into the lumen. Because of the simultaneous activation of K+ and Cl- channels, secretion occurs at a virtually constant membrane potential of about -60 mV. After maximal muscarinic cholinergic stimulation, loss of K+, Cl-, and water results in an approximate 25% reduction in cell volume within 10-15 s after receptor activation. Concomitant with loss of Cl-, there is a loss of HCO3- from the cell, causing a decrease in intracellular pH of 0.1 pH units because of the carbonic anhydrase-mediated conversion of CO2 into H+ and HCO3-. H+ generated from the metabolism and HCO3- production is compensated for by extrusion of H+ by a Na(+)-H+ exchange mechanism, which is responsible for approximately 75% of net Na+ gain that occurs after stimulation. Increased [Na+]i activates the Na(+)-K+ pump, which in turn extrudes Na+ from the cells. In both the unstimulated and stimulated states, cellular production of HCO3- can drive a net uptake of Cl- via the Cl(-)-HCO3- exchange mechanism operating in parallel with the Na(+)-H+ exchanger. The operation of the Cl(-)-HCO3- exchanger is, together with a Na(+)-K(+)-2Cl- cotransport system, essential for maintainance of a high [Cl-]i both in the unstimulated state and during Cl- reuptake.

scholarly journals Regulation of the sodium permeability of the luminal border of toad bladder by intracellular sodium and calcium: role of sodium-calcium exchange in the basolateral membrane.

1981 ◽  
Vol 77 (6) ◽  
pp. 693-712 ◽  
Author(s):  
H S Chase ◽  
Q Al-Awqati
Keyword(s):  
Calcium Transport ◽  
Basolateral Membrane ◽  
Intracellular Sodium ◽  
Toad Bladder ◽  
Transepithelial Transport ◽  
Sodium Permeability ◽  
Cell Calcium ◽  
Luminal Membrane ◽  
Sodium Calcium ◽  
Sodium Gradient

Sodium movement across the luminal membrane of the toad bladder is the rate-limiting step for active transepithelial transport. Recent studies suggest that changes in intracellular sodium regulate the Na permeability of the luminal border, either directly or indirectly via increases in cell calcium induced by the high intracellular sodium. To test these proposals, we measured Na movement across the luminal membrane (th Na influx) and found that it is reduced when intracellular Na is increased by ouabain or by removal of external potassium. Removal of serosal sodium also reduced the influx, suggesting that the Na gradient across the serosal border rather than the cell Na concentration is the critical factor. Because in tissues such as muscle and nerve a steep transmembrane sodium gradient is necessary to maintain low cytosolic calcium, it is possible that a reduction in the sodium gradient in the toad bladder reduces luminal permeability by increasing the cell calcium activity. We found that the inhibition of the influx by ouabain or low serosal Na was prevented, in part, by removal of serosal calcium. To test for the existence of a sodium-calcium exchanger, we studied calcium transport in isolated basolateral membrane vesicles and found that calcium uptake was proportional to the outward directed sodium gradient. Uptake was not the result of a sodium diffusion potential. Calcium efflux from preloaded vesicles was accelerated by an inward directed sodium gradient. Preliminary kinetic analysis showed that the sodium gradient changes the Vmax but not the Km of calcium transport. These results suggest that the effect of intracellular sodium on the luminal sodium permeability is due to changes in intracellular calcium.

CERTAIN ASPECTS OF THE RENAL REGULATION OF BODY COMPOSITION

PEDIATRICS ◽  
1954 ◽  
Vol 14 (6) ◽  
pp. 567-572
Author(s):  
ROBERT E. COOKE
Keyword(s):  
Carbon Dioxide ◽  
Extracellular Space ◽  
Carbonic Acid ◽  
Plasma Concentrations ◽  
Extracellular Volume ◽  
Extracellular Fluid ◽  
Carbon Dioxide Tension ◽  
Plasma Sodium ◽  
Renal Tubules ◽  
Bicarbonate Concentration

THE pH of extracellular fluid is determined by the ratio of the plasma concentrations of bicarbonate ion to carbonic acid, as given in the classical Henderson-Hasselbach equation. [See Equation in Source Pdf] The denominator the carbonic acid concentration, [H2CO3], is proportional to the carbon dioxide tension of the blood. The carbon dioxide tension (pCO2) is primarily dependent upon respiratory function, since metabolism (hence carbon dioxide production) is relatively constant. The numerator of the equation—the bicarbonate concentration of extracellular fluid—is determined by the difference between nonvolatile cations and anions. Since there are almost limitless quantities of bicarbonate available to the organism from cell metabolism, [See Equation in Source Pdf] bicarbonate concentration must change whenever nonvolatile cation (largely sodium) is altered in relation to nonvolatile anion (largely chloride). Thus in most states extracellular bicarbonate concentration is dependent upon the ratio of sodium to chloride in extracellular fluid. The quantity of water filtered at the glomeruli and reabsorbed by the renal tubules each day is approximately 15 times the extracellular volume. The quantity of sodium chloride filtered and reabsorbed daily is approximately 15 times that contained in the extracellular space and 150 times that usually ingested and excreted each day. Therefore, the ratio of plasma sodium to chloride in any steady state is determined by the composition of the renal tubular reabsorbate, as Cushny pointed over 30 years ago. In a sense the kidney perfuses the extracellular space with large quantities of tubular reabsorbate. Tubular reasorbate—the net quantity of materials reabsorbed by the tubules. This term is analogous to glomerular filtrate—the quantity of materials filtered by the glomeruli.

scholarly journals Secretory Potential and Ionic Transport in the Posterior Silk Glands of Bombyx Mori

1988 ◽  
Vol 134 (1) ◽  
pp. 155-171
Author(s):  
I. NAKAGAKI ◽  
S. SASAKI
Keyword(s):  
Membrane Potential ◽  
Basolateral Membrane ◽  
Extracellular Fluid ◽  
Silk Gland ◽  
X Ray ◽  
Gland Cells ◽  
Luminal Membrane ◽  
High K ◽  
Posterior Silk Gland ◽  
Basolateral Membrane Potential

The concentrations of Na, Mg, P, S, Cl, K and Ca in the cytoplasm and lumen of the posterior silk gland cells of Bombyx mori were measured by X-ray microprobe analysis of freeze-dried thin sections. The basal and luminal membrane potentials of the gland cells were measured using microelectrode techniques. The input resistance of the luminal plasma membrane was simultaneously measured by injecting electric current via an intracellular microelectrode. The basolateral membrane potential was −47 ± 1.8mV (S.E.) (N = 46), and the glands exhibited lumen-negative voltages of −6 ± 0.1 mV (S.E.) (N = 40) in the normal state. Increasing the extracellular K+ concentration depolarized the basolateral membrane potential, whereas the membrane potential hyperpolarized when Cl− concentration in the extracellular fluid was increased. There were no significant effects on the membrane potential when NaK+, MgK2+ and CaK2+ concentrations in the extracellular fluid were changed. The representative X-ray spectra showed high K and phosphorus peaks, and low Cl and Mg peaks in the cytoplasm of the normal posterior silk gland cells. The normal glandular lumen showed relatively high K, and low Cl, sulphur, Ca and Mg peaks. Quantitative microprobe values were, for the cytoplasm (mmol kg−1 wet mass, N = 30) Na, 5; Mg, 14; phosphorus, 168; sulphur, 16; Cl, 12; K, 168; Ca, 0.5; and for the lumen (N = 10) Na, 3; Mg, 25; phosphorus, 42; sulphur, 24; Cl, 38; K, 133; Ca, 9.4 in the normal glands. The basal plasma membrane potential was hyperpolarized by 7 mV after stimulation with 5×10−5 mmol l−1 5-hydroxytryptamine (5-HT). Microprobe values for the cytoplasm were (mmol kg−1 wet mass, N = 15) Na, 4; Mg, 13; phosphorus, 160; sulphur, 17; Cl, 8; K, 187; Ca, 0.6 in the stimulated glands. The cytoplasmic [K] increased after stimulation with 5-HT. The basal membrane potential of the gland cells was depolarized by 3 mV after application of a juvenoid, methoprene (10−5 mol l−1). X-ray microprobe values for the cytoplasm were (mmol kg−1 wet mass, N = 15) Na, 7; Mg, 11; P, 170; S, 14; Cl, 23; K, 130; Ca, 3.4 in the treated glands. The cytoplasmic [Ca] and [Cl] increased, while the [K] decreased with methoprene stimulation. The luminal membrane potential of the gland cells was depolarized by 8mV and a simultaneous decrease of luminal membrane resistance was apparent after stimulation with an anti-microfilament reagent, cytochalasin D (2×10−6mol l−1). X-ray microprobe values for the cytoplasm became (mmol kg−1 wet mass, N = 15) Na, 10; Mg, 28; P, 194; S, 22; Cl, 24; K, 148; Ca, 1.2; and for the lumen (N = 15) Na, 14; Mg, 13; phosphorus, 31; sulphur, 30; Cl, 92; K, 122; Ca, 1.1 in the stimulated glands. The cytoplasmic [Ca] and [Cl] increased and [K] decreased, whereas the luminal [Cl] and [sulphur] increased and [Ca] and [Mg] decreased after cytochalasin D stimulation. The reaction products of adenosine triphosphatase activity were found on the luminal and lateral plasma membranes of the posterior silk gland cells. The possible routes of ion transport into the lumen are discussed.

Calcium-activated potassium channels and fluid secretion by exocrine glands

1986 ◽  
Vol 251 (1) ◽  
pp. G1-G13 ◽  
Author(s):  
O. H. Petersen
Keyword(s):  
Single Channel ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Exocrine Glands ◽  
K Channels ◽  
Luminal Membrane ◽  
Channel Opening ◽  
Cell Current ◽  
Cl Channels

Fluid secretion by exocrine glands is regulated by neurotransmitters and hormones. The secretagogues act on the acinar cells by switching on two types of conductance pathways: K+-selective channels in the basolateral membrane and Cl(-)-selective channels localized to the luminal membrane. The K+ channels have been quantitatively characterized in patch-clamp single-channel and whole-cell current-recording studies. Opening of the K+ channels is determined by the membrane potential (depolarization enhances the probability of channel opening), and the intracellular free Ca2+ concentration ([Ca2+]i) (a rise in [Ca2+]i increases the open-state probability). The Cl- channels are also controlled by internal Ca2+ in such a way that an elevation of [Ca2+]i favors opening. Secretagogues evoking an increase in [Ca2+]i activate both sets of channels causing a substantial loss of cellular KCl. KCl is taken up via a Na+-K+-2Cl- cotransport mechanism in the basolateral membrane and the Na+ uptake activates the Na+-K+ pump. In the steady-state stimulated situation the three basolateral transport proteins, the K+ channels, the Na+-K+ pump, and the Na+-K+-2Cl- cotransporter operate together as an electrogenic Cl- pump. Cl- exits into the lumen via the Ca2+-activated Cl- channels and Na+ follows through the paracellular shunt pathway. When stimulation of the acinar cells ceases the K+ and Cl- conductance pathways close and the Na+-K+ pump together with the Na+-K+-2Cl- cotransporter operate as a KCl pump, restoring the intracellular KCl lost initially after start of stimulation and secretion stops.

Dibutyryl cAMP activates bumetanide-sensitive electrolyte transport in Malpighian tubules

1991 ◽  
Vol 261 (3) ◽  
pp. C521-C529 ◽  
Author(s):  
J. L. Hegarty ◽  
B. Zhang ◽  
T. L. Pannabecker ◽  
D. H. Petzel ◽  
M. D. Baustian ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Apical Membrane ◽  
Basolateral Membrane ◽  
Fluid Secretion ◽  
Ringer Solution ◽  
Malpighian Tubules ◽  
Membrane Voltage ◽  
Dibutyryl Camp ◽  
K Secretion ◽  
Transepithelial Voltage

The effects of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) and bumetanide (both 10(-4) M) on transepithelial Na+, K+, Cl-, and fluid secretion and on tubule electrophysiology were studied in isolated Malpighian tubules of the yellow fever mosquito Aedes aegypti. Peritubular DBcAMP significantly increased Na+, Cl-, and fluid secretion but decreased K+ secretion. In DBcAMP-stimulated tubules, bumetanide caused Na+, Cl-, and fluid secretion to return to pre-cAMP control rates and K+ secretion to decrease further. Peritubular bumetanide significantly increased Na+ secretion and decreased K+ secretion so that Cl- and fluid secretion did not change. In bumetanide-treated tubules, the secretagogue effects of DBcAMP are blocked. In isolated Malpighian tubules perfused with symmetrical Ringer solution, DBcAMP significantly hyperpolarized the transepithelial voltage (VT) and depolarized the basolateral membrane voltage (Vbl) with no effect on apical membrane voltage (Va). Total transepithelial resistance (RT) and the fractional resistance of the basolateral membrane (fRbl) significantly decreased. Bumetanide also hyperpolarized VT and depolarized Vbl, however without significantly affecting RT and fRbl. Together these results suggest that, in addition to stimulating electroconductive transport, DBcAMP also activates a nonconductive bumetanide-sensitive transport system in Aedes Malpighian tubules.

Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport

1988 ◽  
Vol 255 (6) ◽  
pp. F1269-F1275 ◽  
Author(s):  
B. A. Stanton ◽  
B. Kaissling
Keyword(s):  
Tap Water ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Extracellular Fluid ◽  
Distal Tubule ◽  
Sodium Absorption ◽  
Transport Capacity ◽  
Volume Depletion ◽  
Osmotic Minipump ◽  
Sodium Uptake

This study was conducted to determine whether a chronic increase in sodium delivery to, and sodium uptake by, the distal tubule stimulates the transport capacity of this tubular segment. To increase the rate of sodium delivery to the distal tubule, furosemide (12 mg/day) was administered continuously to rats by osmotic minipump for 6 days. Volume depletion was prevented by giving the animals a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and tap water to drink. All animals were adrenalectomized and given replacement doses of aldosterone (0.5 microgram.100 g-1.day-1) and dexamethasone (1.2 microgram.100 g-1.day-1) to eliminate changes in adrenal corticosteroid levels. Furosemide was withdrawn 12 h before sodium and potassium transport rates were measured in distal tubules by in vivo microperfusion. We found that increased sodium uptake dramatically enhanced the transport capacity of the distal tubule. Sodium absorption rose from 71.7 to 316.7 pmol.min-1.mm-1, and potassium secretion increased from 30.7 to 73.7 pmol.min-1.mm-1. This response was accompanied by an increase in cell and mitochondrial volume and by proliferation of the basolateral membrane of distal convoluted cells, connecting tubule cells, and principal cells in the distal tubule. We conclude that a chronic increase in sodium uptake by the distal tubule, independent of alterations in extracellular fluid volume and aldosterone levels, stimulates the transport capacity of this nephron segment in part by inducing specific alterations in cell ultrastructure.

scholarly journals Electrogenic NBCe1 (SLC4A4), but not electroneutral NBCn1 (SLC4A7), cotransporter undergoes cholinergic-stimulated endocytosis in salivary ParC5 cells

2008 ◽  
Vol 295 (5) ◽  
pp. C1385-C1398 ◽  
Author(s):  
Clint Perry ◽  
David O. Quissell ◽  
Mary E. Reyland ◽  
Irina I. Grichtchenko
Keyword(s):  
Membrane Trafficking ◽  
Basolateral Membrane ◽  
Fluorescent Microscopy ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Parotid Glands ◽  
Calmodulin Antagonist ◽  
Parotid Acinar Cells ◽  
Early Endosomes ◽  
Gf 109203X

Cholinergic agonists are major stimuli for fluid secretion in parotid acinar cells. Saliva bicarbonate is essential for maintaining oral health. Electrogenic and electroneutral Na+-HCO3− cotransporters (NBCe1 and NBCn1) are abundant in parotid glands. We previously reported that angiotensin regulates NBCe1 by endocytosis in Xenopus oocytes. Here, we studied cholinergic regulation of NBCe1 and NBCn1 membrane trafficking by confocal fluorescent microscopy and surface biotinylation in parotid epithelial cells. NBCe1 and NBCn1 colocalized with E-cadherin monoclonal antibody at the basolateral membrane (BLM) in polarized ParC5 cells. Inhibition of constitutive recycling with the carboxylic ionophore monensin or the calmodulin antagonist W-13 caused NBCe1 to accumulate in early endosomes with a parallel loss from the BLM, suggesting that NBCe1 is constitutively endocytosed. Carbachol and PMA likewise caused redistribution of NBCe1 from BLM to early endosomes. The PKC inhibitor, GF-109203X, blocked this redistribution, indicating a role for PKC. In contrast, BLM NBCn1 was not downregulated in parotid acinar cells treated with constitutive recycling inhibitors, cholinergic stimulators, or PMA. We likewise demonstrate striking differences in regulation of membrane trafficking of NBCe1 vs. NBCn1 in resting and stimulated cells. We speculate that endocytosis of NBCe1, which coincides with the transition to a steady-state phase of stimulated fluid secretion, could be a part of acinar cell adjustment to a continuous secretory response. Stable association of NBCn1 at the membrane may facilitate constitutive uptake of HCO3− across the BLM, thus supporting HCO3− luminal secretion and/or maintaining acid-base homeostasis in stimulated cells.

Nephrogenic Diabetes Insipidus

1996 ◽  
Vol 17 (4) ◽  
pp. 145-146
Author(s):  
Corrine Benchimol
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Duct Cell ◽  
Cell Binding ◽  
Luminal Membrane ◽  
Concentrate Urine ◽  
V2 Receptor ◽  
Final Effect

Nephrogenic diabetes insipidus (NDI) is a disorder, either congenital or acquired, in which antidiuretic hormone (ADH) secretion is normal, but the ability to concentrate urine is reduced because of insensitivity of the collecting tubule to ADH. The antidiuretic action of arginine vasopressin requires binding of the hormone to the renal type V2 receptor on the basolateral membrane of the collecting duct principal cell. Binding results in activation of adenylate cyclase, generation of cAMP, and increased reabsorption of water across the apical membrane of the renal collecting duct cell. The defect in NDI may be located at any of the steps from binding of vasopressin to the final effect of the hormone on the luminal membrane.

ENaC- and CFTR-dependent ion and fluid transport in mammary epithelia

2001 ◽  
Vol 281 (2) ◽  
pp. C633-C648 ◽  
Author(s):  
Sasha Blaug ◽  
Kevin Hybiske ◽  
Jonathan Cohn ◽  
Gary L. Firestone ◽  
Terry E. Machen ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Fluid Transport ◽  
Apical Membrane ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Fluid Secretion ◽  
Equivalent Circuit Analysis ◽  
Mean Values ◽  
Apical Side

Mammary epithelial 31EG4 cells (MEC) were grown as monolayers on filters to analyze the apical membrane mechanisms that help mediate ion and fluid transport across the epithelium. RT-PCR showed the presence of cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial Na+ channel (ENaC) message, and immunomicroscopy showed apical membrane staining for both proteins. CFTR was also localized to the apical membrane of native human mammary duct epithelium. In control conditions, mean values of transepithelial potential (apical-side negative) and resistance ( R T) are −5.9 mV and 829 Ω · cm2, respectively. The apical membrane potential ( V A) is −40.7 mV, and the mean ratio of apical to basolateral membrane resistance ( R A/ R B) is 2.8. Apical amiloride hyperpolarized V A by 19.7 mV and tripled R A/ R B. A cAMP-elevating cocktail depolarized V A by 17.6 mV, decreased R A/ R B by 60%, increased short-circuit current by 6 μA/cm2, decreased R T by 155 Ω · cm2, and largely eliminated responses to amiloride. Whole cell patch-clamp measurements demonstrated amiloride-inhibited Na+ currents [linear current-voltage ( I-V) relation] and forskolin-stimulated Cl−currents (linear I-V relation). A capacitance probe method showed that in the control state, MEC monolayers either absorbed or secreted fluid (2–4 μl · cm−2 · h−1). Fluid secretion was stimulated either by activating CFTR (cAMP) or blocking ENaC (amiloride). These data plus equivalent circuit analysis showed that 1) fluid absorption across MEC is mediated by Na+ transport via apical membrane ENaC, and fluid secretion is mediated, in part, by Cl− transport via apical CFTR; 2) in both cases, appropriate counterions move through tight junctions to maintain electroneutrality; and 3) interactions among CFTR, ENaC, and tight junctions allow MEC to either absorb or secrete fluid and, in situ, may help control luminal [Na+] and [Cl−].

Sign in / Sign up

Export Citation Format

Share Document