抄録
In eukaryotic cells, activation of receptors that couple to the phosphoinositide pathway evoke a biphasic increase in cytosolic free Ca2+ concentration: an initial transient release of Ca2+ from intracellular stores is followed by a sustained phase of Ca2+influx. This influx is generally store-dependent and is required for controlling distinct Ca2+-dependent processes like exocytosis and cell growth. Store-operated Ca2+ entry is often manifest as a non-voltage-gated Ca2+current called ICRAC. CRAC channels are activated by emptying intracellular Ca2+ stores but how stores open the channels is unclear. Three models have been proposed: 1) the vesicular fusion model in which CRAC channels are inserted into the plasma membrane upon store depletion via an exocytotic mechanism; 2) conformational-coupling and secretion-like coupling where InsP3 receptors on the stores physically attach to CRAC channels in the plasma membrane; 3) the diffusible messenger model in which a factor is generated from empty stores and which then opens CRAC channels. We have systematically tested the predictions of each model. Our results are hard to reconcile with the vesicular fusion and coupling-type models. On the other hand, we find that inhibition of lipoxygenase enzymes impairs the activation of ICRAC, raising the possibility that the enzyme might be involved in regulating Ca2+ influx. We are now measuring lipoxygenase activity to see whether it is modulated by store depletion. Our recent results will be described. [Jpn J Physiol 54 Suppl:S47 (2004)]
