FUNCTIONAL GRADIENTS IN MUSCLE-CELLS ISOLATED FROM GALLBLADDER, CYSTIC DUCT, AND COMMON BILE-DUCT

The existence of a gradient inherent to muscle cells of the biliary tract was examined in muscle cells isolated separately from the fundus of the gallbladder, cystic duct, and common bile duct of the dog. Muscle cells, measured in suspension or as single perfused cells, exhibited a proximal-to-distal gradient expressed by the magnitude of response and the sensitivity to hormonal cholecystokinin octapeptide and neural (acetylcholine and methionine-enkephalin) contractile agonists. Measurements in suspensions showed that cells from the fundus 1) were 7-40 times more sensitive to contractile agonists than cells from the cystic duct and 13-200 times more sensitive than cells from the common bile duct and 2) generated greater maximal contraction. The latter was expressed by the ratio of maximal responses (fundus: cystic duct cells, 1.90 ± 0.12, P < 0.001; fundus, common bile duct cells, 1.50 ± 0.07 P < 0.001), which was independent of sensitivity to agonists. Similar results were obtained in measurements on single cells with respect to relative sensitivity and to ratio of maximal responses (fundus: cystic duct cells, 1.80 ± 0.08, P < 0.001; fundus: common bile duct cells, 1.49 ± 0.06, P < 0.001). The ratio of responses to low concentrations of agonists was even higher (three- to fourfold), reflecting both the greater sensitivity and the greater contraction of muscle cells of the fundus. We conclude that a proximal-to-distal biliary gradient exists that is an inherent property of muscle cells from various regions of the biliary tract; the gradient would act to facilitate gallbladder emptying in response to hormonal and neural stimulation.