Subcellular and multicelluar organization of calcium signaling in liver

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Cytosolic Ca2+ ([Ca2+]i) is a ubiquitous intracellular messenger in mammalian cells, and imaging studies of single living cells loaded with fluorescent Ca2+ indicators have demonstrated that the [Ca2+]i changes induced by extracellular agonists are often organized in complex temporal and spatial patterns. A number of hormones that regulate hepatic metabolism, including vasopressin and α1adrenergic agonists, bring about their effects through a rise in [Ca2+]i mediated by the Ca2+-mobilizing second messenger IP3. Imaging studies of isolated hepatocytes have demonstrated that the [Ca+]i responses during continuous exposure to these hormones consist of a series of discrete [Ca+]i spikes, the frequency of which is determined by the dose of agonist. By contrast, the amplitude and kinetics of the individual [Ca+]i spikes are not affected by changing the agonist dose. In addition to the temporal organization in the form of [Ca2+]i oscillations, the [Ca2+]i changes are also spatially organized into regenerative [Ca2+]i waves that propagate throughout the cytoplasm and nucleoplasm of the cell from a discrete plasma membrane locus. These oscillatory [Ca2+]i waves are generated by the complex interplay of [Ca2+]i and IP3 in regulating the gating properties of the IP3- receptor Ca2+ channel, which is located in the endoplasmic reticulum Ca2+ store.