Regulation of K secretion across the porcine gallbladder epithelium.
Porcine gallbladder epithelium from the neck and the fundus of the organ was stripped of serosal muscle and mounted in Ussing chambers to investigate the mechanisms of K secretion. The sensitivity to K channel blockers and regulation by norepinephrine (NE), adenosine 3',5'-cyclic monophosphate (cAMP), and increases in intracellular Ca concentration ([Ca]) were studied. The porcine gallbladder secretes K (approximately 0.8 mu eq/cm2.h) under basal conditions. Mucosal tetraethylammonium (TEA) produced a concentration-dependent increase in short-circuit current (Isc) and inhibited the unidirectional serosal-to-mucosal 86Rb flux JsmRb, resulting in a > 60% reduction in net Rb secretion. In contrast, serosal Ba produced a concentration-dependent decrease in Isc and stimulated JsmRb, resulting in a > 200% increase in net Rb secretion. NE inhibited JsmRb and net Rb secretion in both regions. In the fundic region the mucosal-to-serosal Rb flux (JmsRb) was also significantly increased, suggesting that active K absorption was activated. Exogenous cAMP increased JsmRb and net Rb secretion by > 85% in both regions. This increase in net Rb secretion was blocked by mucosal TEA but unaffected by NE. The Ca ionophore ionomycin also increased JsmRb and net Rb secretion and reduced the Isc by approximately 50%. Neither mucosal TEA nor Ba blocked changes in steady-state Rb secretion induced by ionomycin. Although both serosal Ba and ionomycin produced significant reductions in Isc, the effects of Ba were blocked by ionomycin pretreatment. These findings indicate that basal K secretion occurs through TEA-sensitive apical K channels and is regulated by intracellular cAMP. NE likely reduces K secretion by decreasing intracellular concentration of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
DuVall
M D
MD
Department of Physiology, University of Minnesota, St. Paul 55108.
O'Grady
S M
SM
D000818:Animals; D001464:Barium / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005704:Gallbladder / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D013552:Swine; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D013757:Tetraethylammonium Compounds; D001464:Barium; D015759:Ionomycin; D019789:Tetraethylammonium; D000242:Cyclic AMP; D012413:Rubidium; D011188:Potassium; D009638:Norepinephrine