Electrogenic bicarbonate secretion in mouse gallbladder.
Mouse gallbladders (4 mm2) were investigated using the short-circuit current (Isc) technique. Responses of 50 microA/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.
Martin
L C
LC
Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
Hickman
M E
ME
Curtis
C M
CM
MacVinish
L J
LJ
Cuthbert
A W
AW
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004553:Electric Conductivity; D004848:Epithelium / Q000502:physiology; D005704:Gallbladder / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice
D001639:Bicarbonates; D002712:Chlorides; D007476:Ionophores; D005576:Colforsin; D015759:Ionomycin; D003994:Bucladesine; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine