Calcium channels in hepatocytes

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In living cells, the concentration of cytosolic Ca :+ ([Ca2+]i) is maintained at a level ranging from 50 to 200 nM. The cytosolic Ca 2+ is actively extruded from the cell by a Ca2+-pump present in the plasma membrane and/or by Ca2+/Na + exchange. In resting cells, Ca 2+ is accumulated essentially in the endoplasmic ' reticulum and, to a lesser extent, in mitochondria. The [Ca2+]i is about four orders of magnitude lower than extracellular ([Ca2+]o) and intrareticular [Ca-'+]. In these conditions, small variations in Ca 2+ permeabilities of the plasma membrane or the membrane of the intracellular store can induce fast and large variations of the [Ca2+]i. Ca 2+ can then be used as an intracellular signal for the transduction of extracellular signals carried by hormones or neuromediators_ The resulting increase in [Ca2+]i modulates a number of cellular functions such as contraction, secretion and activation of the enzymes of cell metabolism. It is well known that the initial phase of the [Ca2+]i rise initiated by hormones results essentially from the release of Ca ,-+ accumulated in the intracellular store. The sustained phase is due to an influx of extracellular Ca :+ [1,2]. In a stimulated cell, the two Ca 2+ fluxes coming from an intracellular store and from the extracellular medium converge in the cytosol to maintain an elevated [Ca2+]i. The mechanism of the diffusional transport of Ca 2+ through the biological membranes has been the subject of a number of studies. In many cases, it has been shown to result from the activation of specific channels. Different types of Ca 2+ channels have been found in eucaryotes. Those gated by the membrane potential are called voltage-operated channels (VOCs). Others, opened by the binding of ligands (hormones or neurotransmitters) to specific receptors are called receptor-operated channels (ROCs). The VOCs studied by electrophysiological techniques have been differentiated into: T-(transient), N-(neuronal) and L-(long-lasting) channels_ N-channels are present only in neuronal cells, whereas Tand L-channels have been identified in most excitable cells. The L-type channel can be modulated by hormones through different cellular effectors such as cAMP-dependent or cGMP-dependent protein kinases, protein kinase C and G-proteins (see Ref. 3). These L-channels are inhibited by specific inhibitors,