Apical Ca2+ activated K+ Channels in Mouse Lacrimal Acinar Cells

Abstract

Fluid secretion of salivary glands relies on intracellular calcium transients activating calcium dependent Cl− conductances in the luminal membrane of acinar cells. Older parotid acinar cell models place Ca2+-activated K+ channels into the basolateral membrane because early studies found Ca2+-activated K+ channel activity in cell-attached patches targeting this membrane domain. Recently we have used the combination of whole cell patch clamp electrophysiology, spatially localized flash photolysis of caged Ca2+ and temporally resolved digital Ca2+ imaging to show that Ca2+ -activated K+ channels colocalize with Cl− channels and occur in much higher density in the luminal membrane of parotid acinar cells compared to the basal. This finding provided evidence that supported a new mathematical model in which optimal fluid secretion requires significant K+ conductance inserted into the luminal membrane. The aim of the present study was to test the localization of Ca2+ -dependent K+ channels in acinar cells from a different tissue, the lacrimal gland. Our initial experiments have shown both intermediate (IK) and big conductance (BK) Ca2+-activated K+ currents in these cells, although the abundance of IK conductance is less when compared to parotid. Flash-induced localized Ca2+ elevations at the luminal membrane resulted in a robust increase in K+ and Cl− currents. The K+ current evoked by apical photolysis was abolished by 10 μM paxilline, a specific inhibitor of BK channels. Our failure to activate IK in these experiments suggests that the role of IK in lacrimal acinar cells is smaller compared to parotid. In contrast, when the [Ca2+] was increased at the basal plasma membrane, no increase in either K+ or Cl− currents was evoked. These data indicate that the density of large conductance Ca2+ activated K+ channels appears higher in the apical versus basal plasma membrane.