CO2 permeability and bicarbonate transport in microperfused interlobular ducts isolated from guinea-pig pancreas

Permeabilities of the luminal and basolateral membranes of pancreatic duct cells to CO2 and HCO3− were examined in interlobular duct segments isolated from guinea-pig pancreas. Intracellular pH (pHi) was measured by microfluorometry in unstimulated, microperfused ducts loaded with the pH-sensitive fluoroprobe 2′7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF).When HCO3−/CO2 was admitted to the bath, pHi decreased transiently as a result of CO2 diffusion and then increased to a higher value as a result of HCO3− uptake across the basolateral membrane by Na+-HCO3− cotransport.When HCO3−/CO2 was admitted to the lumen, pHi again decreased but no subsequent increase was observed, indicating that the luminal membrane was permeable to CO2 but did not allow HCO3− entry to the cells from the lumen. Only when the luminal HCO3− concentration was raised above 125 mm was HCO3− entry detected. The same was true of duct cells stimulated with forskolin.Recovery of pHi from an acid load, induced by exposure to an NH4+ pulse, was dependent on basolateral but not luminal Na+ and could be blocked by basolateral application of methylisobutylamiloride and H2DIDS. This indicates that the Na+-H+ exchangers and Na+-HCO3− cotransporters are located exclusively at the basolateral membrane.In the presence of HCO3−/CO2, substitution of basolateral Cl− with glucuronate caused larger increases in pHi than substitution of luminal Cl−. This suggests that the anion exchanger activity in the basolateral membrane is greater than that in the luminal membrane.We conclude that the luminal and basolateral membranes are both freely permeable to CO2, but while the basolateral membrane has both uptake and efflux pathways for HCO3−, the luminal membrane presents a significant barrier to the re-entry of secreted HCO3−, largely through the inhibition of the luminal anion exchanger by high luminal HCO3− concentrations

Building joint capacity: The role of European agencies in the management of transboundary crises

This paper focuses on the growing role of European Union (EU) agencies in the management of trans-boundary crises. It makes this development explicit, demonstrating that the emergence of multiple agencies with specific crisis preparation or response tasks has transformed the EU’s crisis management arrangements and structures. By relying on both the literature on crisis management and EU agencies, the paper discusses the advantages and disadvantages of the existing (and evolving) multi-agency model, comparing it with a more centralized, singleagency model. It reflects on the role of EU agencies within the expanding contours of the EU’s emerging crisis capacity and the most appropriate way forward for effective and legitimate crisis management at the EU level, thus contributing to both the debate on the EU’s role in crisis management and the delegation of tasks to specialized EU agencies