Subcellular organization of calcium signalling in hepatocytes and the intact liver.
Hepatocytes respond to inositol 1,4,5-trisphosphate (InsP3)-linked agonists with frequency-modulated oscillations in the intracellular free calcium concentration ([Ca2+]i), that occur as waves propagating from a specific origin within each cell. The subcellular distribution and functional organization of InsP3-sensitive Ca2+ pools has been investigated, in both intact and permeabilized cells, by fluorescence imaging of dyes which can be used to monitor luminal Ca2+ content and InsP3-activated ion permeability in a spatially resolved manner. The Ca2+ stores behave as a luminally continuous system distributed throughout the cytoplasm. The structure of the stores, an important determinant of their function, is controlled by the cytoskeleton and can be modulated in a guanine nucleotide-dependent manner. The nuclear matrix is devoid of Ca2+ stores, but Ca2+ waves in the intact cell propagate through this compartment. The organization of [Ca2+]i signals has also been investigated in the perfused liver. Frequency-modulated [Ca2+]i oscillations are still observed at the single cell level, with similar properties to those in the isolated hepatocyte. The [Ca2+]i oscillations propagate between cells in the intact liver, leading to the synchronization of [Ca2+]i signals across part or all of each hepatic lobule.
Thomas
A P
AP
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Renard-Rooney
D C
DC
Hajnóczky
G
G
Robb-Gaspers
L D
LD
Lin
C
C
Rooney
T A
TA
D000818:Animals; D002118:Calcium / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D002118:Calcium