Inositol trisphosphate and calcium oscillations

Abstract

InsP3 has two important functions in generating Ca2+ oscillations. It releases Ca2+ from the internal store and it can contribute to Ca2+ entry. A hypothesis has been developed to describe a mechanism for Ca2+ oscillations with particular emphasis on the way agonist concentration regulates oscillator frequency. The main idea is that the InsP3 receptors are sensitized to release Ca2+ periodically by cyclical fluctuations of Ca2+ within the lumen of the endoplasmic reticulum. Each time a pulse of Ca2+ is released, the luminal level of Ca2+ declines and has to be replenished before the InsP3 receptors are resensitized to deliver the next pulse of Ca2+. It is this loading of the internal store that explains why frequency is sensitive to external Ca2+ and may also account for how variations in agonist concentration are translated into changes in oscillation frequency. Variations in agonist-induced entry of external Ca2+, which can occur through different mechanisms, determine the variable rates of store loading responsible for adjusting the sensitivity of the InsP3 receptors to produce the periodic pulses of Ca2+. The Ca2+ oscillator is an effective analogue-to-digital converter in that variations in the concentration of the external stimulus are translated into a change in oscillator frequency.

Improvement of mouse embryo quality by myo-inositol supplementation of IVF media

“…This was expected by data on myoIns uptake in mouse preimplantation embryos and its incorporation into phosphatidylinositides (PtdIns) [22]. A higher availability of PtdIns may increase the production of intracellular second messengers and upregulate a number of cellular functions including proliferation [3,15,38,43]. Since myoIns has been reported to increase PKB/Akt phosphorylation in mouse skeletal muscle cells [8], among signal transduction mechanisms possibly induced as a consequence of myoIns medium supplementation and by increased PtdIns availability, is the phosphorylation of this enzyme [27], the activation and nuclear mobilitation of which promotes proliferation activity of mouse embryo blastomeres [14].…”

“…Myo-inositol (myoIns) is the major component of a group of exahydrocyclohexanes (C 6 H 12 O 6 ) with defined roles in eukaryotic cells, including mammalian oocytes and early embryos, as a precursor of phosphoinositides, membrane components, anchor molecules (reviewed by [35]), signaling molecules (reviewed by [3,11]), and as hyperosmotic stress protectant [46].…”

IP3 Receptors: Toward Understanding Their Activation

“…Persuasive evidence suggests that Ca 2þ release by RyR may be terminated before Ca 2þ stores are entirely depleted because luminal Ca 2þ is required to maintain RyR activity (Györke and Györke 1998;Launikonis et al 2006;Jiang et al 2008), possibly via its interaction with calsequestrin, a luminal high-capacity Ca 2þ -binding protein (Launikonis et al 2006;Terentyev et al 2006). A similar scheme has been proposed to account for two features of IP 3 -evoked Ca 2þ release: the initiation of Ca 2þ release after the quiescent interspike interval during repetitive Ca 2þ spikes (Berridge 2007) and quantal Ca 2þ release via IP 3 R. The latter describes the situation wherein unidirectional Ca 2þ efflux from intracellular stores terminates before the stores have fully emptied after stimulation with submaximally effective concentrations of IP 3 without loss of their ability to respond to a further increase in IP 3 concentration (Muallem et al 1989;Meyer and Stryer 1990;Taylor and Potter 1990;Oldershaw et al 1991;Bootman et al 1992;Brown et al 1992;Combettes et al 1992;Ferris et al 1992;Hirota et al 1995). The proposal is that luminal Ca 2þ sets the gain on the regulation by cytosolic IP 3 and Ca 2þ , so that as the luminal free Ca 2þ concentration falls, it causes the sensitivity of the IP 3 R to IP 3 to fall until, as Ca 2þ leaks from the ER, the IP 3 R closes despite the continued presence of cytosolic IP 3 and residual Ca 2þ within the ER (Irvine 1990).…”

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

“…Others have suggested ATP release/purinergic signalling may play a role in supporting Ca 2þ oscillations. 14 In blood-brain barrier endothelial cells, inhibiting hemichannels or ATP signalling blocked bradykinin-triggered Ca 2þ oscillations and prevented vascular barrier dysfunction. 15,16 Vascular cells express several Cxs, including Cx37, Cx40, and Cx43 in endothelial cells, and Cx37, Cx43, and Cx45 in SMCs.…”