Intracellular calcium in the isolated rat liver: correlation to glucose release, K(+) balance and bile flow

Abstract

This study correlates whole organ measurements of intracellular calcium concentration ([Ca(2+)](i)) with hormone-induced (epinephrine, vasopressin) changes of liver functions (glucose release, K(+) balance and bile flow). [Ca(2+)](i) was measured in the isolated perfused rat liver using the sensor Fura-2 and applying liver surface fluorescence spectroscopy. The technique was improved by (i) minimizing biliary elimination of the sensor by employing a rat strain deficient in canalicular organic anion transport (TR(-) mutation) and (ii) by correcting for changes of interfering intrinsic organ fluorescence that was shown to depend on the oxidation-reduction state (NAD(P)H content) of the organ. Epinephrine (50 nM) elicits an instantaneous peak rise of [Ca(2+)](i) to approx. 400 nM, followed by a sustained elevation that depends on the presence of extracellular Ca(2+). The rise of [Ca(2+)](i) coincides with initiation of glucose release, transient K(+) uptake, and transient stimulation of bile flow. Vasopressin (2 nM) exerts qualitatively similar effects. The transient rise of bile flow is attributed to Ca(2+)-mediated contraction of the pericanalicular actin-myosin web of hepatocytes.