Selective blockage of cell membrane K conductance by an antisecretory agent in guinea-pig gallbladder epithelium.

Loperamide inhibits PGE1-induced electrogenic HCO3 secretion in guinea-pig gallbladder. Underlying changes in epithelial cell membrane properties were investigated using intracellular microelectrode techniques in vitro. In the absence of PGE1, mucosal loperamide (10(-4) mol/l) reversibly depolarized both cell membranes by approximately 6 mV. The apparent ratio of membrane resistances (Ra/Rb) remained unchanged and so did voltage responses to luminal Cl removal and Na reduction. The depolarizing response to elevation of luminal K concentration from 5 to 76 mmol/l was decreased from 13 to 8 mV. In the presence of 1 PGE1, the apical membrane is mainly permeable to Cl and HCO3. Under these conditions, loperamide reduced membrane potentials by approximately 10 mV, Ra/Rb remaining constant at approximately 0.4. Effects on voltage responses to changes in luminal Na or K concentration were unchanged. Responses to luminal Cl removal (transient depolarization) were greatly enhanced (from 22 to 42 mV) as predictable from the fall in K permeability that hinders Cl efflux from cell into lumen. Less marked but significant effects were obtained with 10(-5) mol/l (mucosal side) and serosal loperamide (10(-4) mol/l). We suggest that loperamide inhibits electrogenic HCO3 secretion by reducing apical membrane K permeability. The resulting depolarization diminishes the driving force for conductive anion efflux from cell into lumen. This conclusion is supported by the ability of luminal K elevation to mimick loperamide inhibition of the secretory flux of HCO3 (pH-stat experiments).