InsP₃-induced Ca²⁺ excitability of the endoplasmic reticulum

Oscillations in intracellular Ca²⁺ can be induced by a variety of cellular signalling processes (Woods et al., 1986; Berridge 1988; Jacob et al., 1988) and appear to play a role in secretion (Stojilković et al., 1994), fertilization (Miyazaki et al., 1993), and smooth muscle contraction (lino and Tsukioka, 1994). Recently, great progress has been made in understanding the mechanisms involved in a particular class of Ca²⁺ oscillation, associated with the second messenger inositol 1,4,5-trisphosphate (InsP₃) (Berridge, 1993). Working in concert with intracellular Ca²⁺, InsP₃ controls Ca²⁺ release via the InsP₃ receptor in the endoplasmic reticulum (ER) (Berridge and Irvine, 1989). The IP₃ receptor is regulated by its coagonists InsP₃ and Ca²⁺, which both activate and inhibit Ca²⁺ release (Finch et al., 1991; Bezprozvanny et al., 1991; De Young and Keizer, 1992). These processes, together with the periodic activation of Ca²⁺ uptake into the ER, have been identified as key features in the mechanism of InsP₃-induced Ca²⁺ oscillations in pituitary gonadotrophs (Li et al., 1994), Xenopus laevis oocytes (Lechleiter and Clapham, 1992; Atri et al., 1993), and other cell types (Keizer and De Young, 1993). Earlier discussions and models of InsP₃-induced Ca²⁺ oscillations focused on the nature and number of internal releasable pools of Ca²⁺ (Goldbeter et al., 1990; Swillens and Mercan, 1990; Somogyi and Stucki, 1991), the importance of oscillations in InsP₃ (Meyer and Stryer, 1988), and other issues not based on detailed experimental findings in specific cells types. In this review we briefly summarize recent experimental findings dealing with InsP₃-induced Ca²⁺ excitability of the ER and describe a detailed, quantitative model that explains how intracellular Ca²⁺ oscillations occur (De Young and Keizer, 1992; Li et al., 1995b).