³⁶Cl bomb peak: comparison of modeled and measured data

The extensive nuclear bomb testing of the fifties and sixties and the final tests in the seventies caused a strong 36Cl peak that has been observed in ice cores world-wide. The measured 36Cl deposition fluxes in eight ice cores (Dye3, Fiescherhorn, Grenzgletscher, Guliya, Huascarán, North GRIP, Inylchek (Tien Shan) and Berkner Island) were compared with an ECHAM5-HAM general circulation model simulation (1952–1972). We find a good agreement between the measured and the modeled 36Cl fluxes assuming that the bomb test produced global 36Cl input was ~80 kg. The model simulation indicates that the fallout of the bomb test produced 36Cl is largest in the subtropics and mid-latitudes due to the strong stratosphere-troposphere exchange. In Greenland the 36Cl bomb signal is quite large due to the relatively high precipitation rate. In Antarctica the 36Cl bomb peak is small but is visible even in the driest areas. The model suggests that the large bomb tests in the Northern Hemisphere are visible around the globe but the later (end of sixties and early seventies) smaller tests in the Southern Hemisphere are much less visible in the Northern Hemisphere. The question of how rapidly and to what extent the bomb produced 36Cl is mixed between the hemispheres depends on the season of the bomb test. The model results give an estimate of the amplitude of the bomb peak around the globe.

³⁶Cl bomb peak: comparison of modeled and measured data

The extensive nuclear bomb testing of the fifties and sixties and the final tests in the seventies caused a strong 36Cl peak that has been observed in ice cores world-wide. The measured 36Cl deposition fluxes in eight ice cores (Dye3, Fiescherhorn, Grenzgletscher, Guliya, Huascarán, North GRIP, Inylchek (Tien Shan) and Berkner Island) were compared with an ECHAM5-HAM general circulation model simulation (1952–1972). We find a good agreement between the measured and the modeled 36Cl fluxes assuming that the bomb test produced global 36Cl input was ~80 kg. The model simulation indicates that the fallout of the bomb test produced 36Cl is largest in the subtropics and mid-latitudes due to the strong stratosphere-troposphere exchange. In Greenland the 36Cl bomb signal is quite large due to the relatively high precipitation rate. In Antarctica the 36Cl bomb peak is small but is visible even in the driest areas. The model suggests that the large bomb tests in the Northern Hemisphere are visible around the globe but the later (end of sixties and early seventies) smaller tests in the Southern Hemisphere are much less visible in the Northern Hemisphere. The question of how rapidly and to what extent the bomb produced 36Cl is mixed between the hemispheres depends on the season of the bomb test. The model results give an estimate of the amplitude of the bomb peak around the globe.

Evidence of Na-K-Cl cotransport in airway smooth muscle

The presence of the Na-K-Cl cotransporter in airway smooth muscle was investigated by measuring 86Rb+ (as a marker for K+) and 36Cl- fluxes in the guinea pig trachealis. K+ uptake consisted of 1) a bumetanide- and furosemide-sensitive component, 2) a ouabain-sensitive component, and 3) a bumetanide- and ouabain-insensitive component. Bumetanide and furosemide inhibited K+ uptake with IC50s of 0.18 and 5.6 microM, respectively. Bumetanide-sensitive K+ uptake was reduced by the isosmotic replacement of extracellular Na+ and Cl- with choline and I-, respectively. Bumetanide caused a reduction in Cl- uptake, and the ratio of bumetanide-sensitive K+ to Cl-uptake was approximately 1:1.75. Bumetanide caused a decrease in 86Rb+ efflux, suggesting that the Na-K-Cl cotransporter mediates both K+ influx and efflux in airway smooth muscle. Ouabain caused an increase in bumetanide-sensitive 86Rb+ efflux from the guinea pig trachealis, which was prevented by exposure to a low-Na+ medium, suggesting that Na-K pump inhibition stimulates outward Na-K-Cl cotransport as a result of an increase in intracellular Na+ content.

Regulatory volume decrease in HL-60 cells: importance of rapid changes in permeability of Cl- and organic solutes

Results obtained through the use of inhibitors and isotope flux and equilibration techniques indicate that the regulatory volume decrease (RVD) response of human promyelocytic leukemic HL-60 cells occurs largely through the efflux of K+ and Cl- through separate conductive membrane pathways. These "channels" differ pharmacologically and in their modes of activation from those described in lymphocytes and Ehrlich ascites tumor cells. With use of measured 86Rb+ and 36Cl- fluxes, together with a diffusion kinetic model, the membrane potential (Em) and apparent K+ and Cl- permeabilities (PK and PCl) were estimated under various isotonic and hypotonic conditions. Under isotonic (300 mosM) conditions, Em is close to the Nernst potential for K+ and PCl is < 0.1 PK. Rapid and steeply graded increases in the measured Cl- efflux rate and calculated PCl occur with decreasing tonicity, with the largest increases at tonicities < 80% of isotonic. K+ efflux and the apparent PK increase only modestly with decreasing tonicity. At 50% tonicity, PCl rises to nearly 10 times PK, which should cause substantial membrane depolarization, with Em approaching the Nernst potential for Cl-. Gramicidin treatment markedly accelerates the rate of RVD and net 36Cl- efflux in hypotonic Na(+)-and Cl(-)-free media, providing further evidence that PK is rate limiting during RVD. K+ loss exceeds Cl- loss during RVD, and the total loss of K+ and Cl- is insufficient to account for the observed degree of volume recovery in 50% tonicity media, indicating that other (organic) osmolytes must take part in the HL-60 cell RVD response.

Galanin-induced alteration of electrolyte transport in the rat intestine

Effects of rat and porcine galanin on rat intestinal ion transport were examined in vitro. In the rat distal colon, a sustained increase in short-circuit current (Isc) was produced by the serosal addition of rat galanin at a concentration as low as 10(-9) M, and a maximal increment was observed at 10(-7) M. Porcine galanin was approximately 100 times less potent than rat galanin. In the rat jejunum, rat galanin produced only a slight and transient decrease in basal Isc. The response to rat galanin was not influenced by atropine, hexamethonium, or amiloride, but was virtually abolished by tetrodotoxin or furosemide. Rat galanin did not significantly influence the increase in Isc elicited by electrical field stimulation in the rat colon and jejunum. Transmural unidirectional 22Na and 36Cl fluxes in the rat colonic mucosa were measured under short-circuited conditions, and rat galanin significantly decreased net sodium and net chloride absorption. These findings suggest that galanin acts as a secretory modulator in the rat colon via noncholinergic neural transmission.

Actions of mercurials on cell volume regulation of dissociated MDCK cells

The mercurial, p-chloromercuribenzoylsulfonate (PCMBS), blocks volume recovery of dissociated, osmotically swollen, Madin-Darby canine kidney cells (MDCK) and, at higher concentrations, induces substantial swelling. In the absence of Na+ the rate of volume recovery is, in contrast, substantially increased. PCMBS does not inhibit the "normal" volume-regulating pathways, K+ and Cl- conductances. Rather, its blocking action is due to substantial activation of Na+ and K+ permeabilities, especially the former. Consequently, the normal reshrinking mechanism, loss of KCl, is counterbalanced by PCMBS-induced gains of NaCl. In isotonic cells, PCMBS, at higher concentrations, induces cell swelling, indicating that Cl- permeability is also increased, a conclusion confirmed by direct measurement of 36Cl- fluxes. HgCl2 produces similar effects except that it is more potent and more rapid in its action. Activation of conductive ion permeabilities to Na+, K+, and Cl- are associated with appropriate changes in membrane potential. A small bumetanide-sensitive swelling component (Na(+)-Cl- cotransport) is activated by HgCl2 but not by PCMBS. Another effect is elevation of cytoplasmic Ca2+, apparently by mobilization from internal stores. Some of the functional sites (Na+ and K+) appear to be located externally, rapidly accessible to both HgCl2 and PCMBS, whereas others (Cl- and Ca2+) appear to be internal, rapidly accessible to the permeant HgCl2 but slowly to relatively impermeant PCMBS. In conclusion, the disturbances of volume regulation are largely due to the increases in conductive ion fluxes.

Chemotactic peptide effects on intestinal electrolyte transport

The bacterial-derived chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) increases short-circuit current (Isc) and arachidonic acid metabolism (AAM) in rabbit ileum and distal colon. Serosal (s) or mucosal (m) addition of fMLP transiently increases Isc. Half-maximally effective dose and maximal increases in Isc were 32 nM and 84 microA/cm2 in ileum and 234 nM and 80 microA/cm2 in colon, respectively. Piroxicam, a cyclooxygenase inhibitor, diminished the Isc response by 97% in colon and 69% in ileum. Changes in Isc were dependent on Cl- and HCO3- in the bathing media. In ileum, fMLP inhibited m-to-s 36Cl- fluxes and stimulated s-to-m 36Cl- fluxes. These changes in Cl- flux were also inhibited by piroxicam. fMLP stimulated prostaglandin E2 (PGE2) release in intact tissue and in isolated subepithelial components. Increased tissue adenosine 3',5'-cyclic monophosphate levels were detected in intact tissue but not in isolated components. Previous desensitization of ileum to PGE1 inhibited fMLP stimulation of Isc in ileum by 88%. Desensitization to fMLP in ileum failed to alter the effect of PGE1 (10 microM) on Isc. In isolated microsomal membranes of ileal enterocytes, fMLP binding sites could not be demonstrated, suggesting that fMLPs action was initially mediated via stimulation of nonepithelial cell cyclooxygenase activity. The above results indicate that fMLP stimulates net secretion in both ileum and colon probably by the activation of AAM.

Membrane site of action of CO2 on colonic sodium absorption

Increases in ambient CO2 tension increase colonic sodium absorption by increasing mucosal to serosal sodium flux. We examined the membrane site of CO2 action by utilizing the polyene antibiotic nystatin to create aqueous pores in the apical membrane. Under these conditions, the basolateral rather than the apical membrane is rate limiting for sodium absorption. Pairs of stripped rat distal colonic segments were mounted in modified Ussing chambers in a Ringer-HCO3 solution gassed with either 3% CO2-97% O2 or 11% CO2-89% O2. Mucosal-to-serosal 22Na and 36Cl fluxes were measured under short-circuited conditions, and ouabain-sensitive absorption was calculated before and after the addition of mucosal nystatin 300 U/ml. Ouabain-sensitive sodium absorption was fivefold greater at 11% CO2 than at 3% CO2 before nystatin addition. Nystatin increased short-circuit current (Isc), transcolonic conductance (Gt) and ouabain-sensitive sodium absorption at 3% CO2 but only increased Isc and Gt at 11% CO2. The levels of sodium absorption at 3% and 11% CO2 after nystatin were equal and identical to the level measured at 11% CO2 in the absence of nystatin. Ouabain-sensitive chloride absorption was similar at 3% and 11% CO2 in the absence of nystatin and was not affected by nystatin addition. These findings suggest that ambient CO2 tension affects colonic sodium absorption by a selective action at the apical membrane.

Furosemide reduces insulin release by inhibition of Cl- and Ca2+ fluxes in beta-cells

The effect of furosemide on insulin release, glucose oxidation, 36Cl- fluxes, and 45Ca2+ uptake was studied in isolated, beta-cell-rich pancreatic islets from ob/ob mice. Low concentrations of furosemide (0.01-0.1 mM) reduced the glucose-induced insulin release, whereas high doses (1-10 mM) increased basal and glucose-induced release. Furosemide at concentrations that reduced glucose-induced insulin release (0.01-0.1 mM) did not affect the islet production of 14CO2 from D-[U-14C]glucose. The influx rate and equilibrium content of 36Cl- were reduced by furosemide, whereas the basal and glucose-stimulated 36Cl- efflux rates were unaffected. The glucose-induced (10 mM) uptake of 45Ca2+ was inhibited by furosemide. It is suggested that the diabetogenic action of furosemide may be due, at least in part, to direct inhibition of insulin release from the pancreatic beta-cells. This may be caused primarily by inhibition of an inwardly directed Cl- pump, leading to a reduced transmembrane electrochemical gradient for chloride in the beta-cells. This reduced gradient in combination with unaltered Cl- permeability may lead to decreased total outward Cl- transport, a factor associated with stimulated calcium uptake and insulin release.