CA2+ WAVES ARE ORGANIZED AMONG HEPATOCYTES IN THE INTACT ORGAN

Hormone-induced increases in cytosolic Ca2+ (Ca-i(2+)) begin as Ca-i(2+) waves in cells isolated from most types of tissue (1, 11), but whether such waves actually occur in vivo is unknown. To investigate this, we examined vasopressin-induced Ca-i(2+) signals in hepatocytes within the perfused rat liver. Using confocal fluorescence video microscopy, we found that increases in Ca-i(2+) began as waves that usually originated in hepatocytes near central venules, then spread opposite to the direction of blood flow, to hepatocytes near portal venules. We used immunochemistry to determine that the liver vasopressin V-1a receptor is most concentrated among hepatocytes in the pericentral region, providing the mechanism by which Ca-i(2+) waves originate there. Pericentral-to-periportal Ca-i(2+) waves may direct peristaltic flow of bile, since Ca-i(2+) induces contraction of the apical pole of hepatocytes and since peristaltic contractions in liver also occur in a pericentral-to-periportal direction. The organization of Ca-i(2+) waves among cells in intact tissue may be a means by which an integrative, organ-level response is provided in response to hormonal stimuli.