Potassium transport by pancreatic and parotid zymogen granule membranes

Abstract

Zymogen granules that were stable at physiological conditions of pH, ionic strength, and temperature were isolated from the rat pancreas and parotid. The cation permeability of these granules was evaluated to characterize the mechanism of secretagogue-stimulated fluid secretion by acinar cells. Granule swelling and lysis provide a measure of the rate of cation transport, since the use of ionophore combinations such as tripropyltin and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) will render cation conductance the rate-limiting step for salt influx. This technique supplies evidence for the existence of K+ conductance in the granule membrane. The pancreatic and parotid granules have a K+-selective conductance that is not inhibited by the K+ channel blockers barium, tetraethylammonium, quinidine, cesium, or 4-aminopyridine. Furthermore, the intragranular pH of pancreatic zymogen granules was measured to be approximately 6.5 and was identified as a factor that modulates the K+ conductance. Although the pancreatic and parotid granules were qualitatively identical, quantitatively the relative K+ transport rate constant was over twofold higher for the parotid than for the pancreatic granules. The zymogen granule K+ conductance may have an important role in active K+ secretion by exocrine glands, which is prominent in the parotid after stimulation with beta-adrenergic agents.

Immunolocalization of Anion Exchanger AE2, Na+/H+ Exchangers NHE1 and NHE4, and Vacuolar Type H+-ATPase in Rat Pancreas

“…Active H ϩ pumping by V-ATPases is generally held responsible for acidification of intracellular compartments. Our data suggest that the acidic intragranular pH previously reported (Gasser et al 1988) reflects granule acidification generated by a V-ATPase. What could be the physiological role of an acidic granule pH?…”

Renin secretion from permeabilized juxtaglomerular cells requires a permeant cation

“…Moreover, the assumed potassium entry pathway in the renin granule membrane shares a number of characteristics with that of isolated pancreatic and parotid zymogen granules: both are insensitive to barium, TEA and quinidine, and the proposed cation selectivity patterns of the granule membranes are identical [4]. In pancreatic zymogen granule membranes there is evidence for potassium transport that is inhibited by ATP [3].…”

“…Experimental evidence obtained in studies of various secretory cells suggests that chloride ions are an essential component in the stimulation-secretion coupling initiated by intracellular second messengers or extracellular agonists [2,16]. Fuller et al [2] proposed a model for zymogen granules where agonist binding leads to a flow of KCl into the secretory granules through K + channels (inhibited by Ba 2+ and quinidine) and through Cl -channels (inhibited by DIDS) [4]. With minor differences, similar results have been reported in studies of permeabilized rat parotid acini [20].…”

Effects of cholinergic and α-adrenergic agonists on the monovalent ion content of rat submandibular gland acinar cells studied by X-ray microanalysis

“…This suggests that the limiting membranes are permeable to these ions to the extent that there is a quick equilibration among the various organelles (Gasser et al 1988;Izutsu et al 1994). All the organelles lose K and Cl upon stimulation, including secretory granules.…”