Hormonal regulation of cytosolic calcium levels in the liver.
Regulation of free cytosolic Ca2+ level in the liver is important because of the many Ca2(+)-dependent processes in the liver, such as respiration, gluconeogenesis, glycogenolysis, cell division, etc. Free cytosolic Ca2+ levels are maintained in the unstimulated state below 1 microM. This level is maintained by an outwardly directed Ca2(+)-ATPase in the plasma membrane, sequestration into the endoplasmic reticulum by a Ca2(+)-ATPase, binding of Ca2+ to specific Ca2(+)-binding proteins, such as calmodulin, and membrane potential-driven uptake into the mitochondria. Upon stimulation by hormones which act by increasing cytosolic free Ca2+ levels, both Ca2+ influx and the release of stored Ca2+ from the endoplasmic reticulum contribute to the increases in cytosolic free Ca2+ levels. The exact mechanism(s) by which these events occur is being intensively studied and debated. Here, it is suggested that hormones activate through a second messenger 1) a ligand-gated Ca2+ channel present in the plasma membrane, and 2) a different Ca2+ channel present in the endoplasmic reticulum. As a result, cytosolic-free Ca2+ levels increase and Ca2(+)-dependent processes are activated. A role for the cytoskeleton in the activation of the ryanodine-binding channel is proposed. Future studies are needed to identify the molecular identity of the hepatic ryanodine receptor and to define the role of the cytoskeleton in signal transduction.
Department of Physiology and Cell Biology, University of Texas Medical School at Houston 77225, USA.
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Kraus-Friedmann
D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D005765:Gastrointestinal Agents; D005934:Glucagon; D000252:Calcium-Transporting ATPases; D002118:Calcium