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Department of Pharmacology, University of Cambridge, Cambridge CB2 1QJ, United Kingdom
Mouse gallbladders (4 mm2) were investigated using the short-circuit current (Isc) technique. Responses of 50 µA/cm2 were obtained in response to forskolin and agents that stimulated the adenylate cyclase system (IBMX and dibutyryl-cAMP). The calcium ionophore ionomycin increased Isc to 30% of the forskolin-stimulated increase. The forskolin-dependent current was inhibited 40% by acetazolamide but was insensitive to furosemide. Forskolin responses were dependent on the presence of bicarbonate ions; removal from both sides of the membrane or the basolateral side alone caused a significant reduction in responses. Removal of chloride ions from the basolateral side had no effect, while removal from the apical side caused a significant reduction in the forskolin responses, but only by 30%. It is argued that the remaining current (70%) cannot result from a parallel arrangement of a chloride channel and a chloride-bicarbonate exchanger and that bicarbonate is secreted through the apical membrane by a predominantly conductive mechanism. Apparently, forskolin converts a near electrically silent epithelium to an electrogenically secreting tissue.
electrogenic transport; forskolin; acetazolamide
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