INSP(3)-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 (Stojilkovic et al., 1994), fertilization (Miyazaki et al., 1993), and smooth muscle contraction (Iino 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 (InsP(3)) (Berridge, 1993). Working in concert with intracellular Ca2+, InsP(3) controls Ca2+ release via the InsP(3) receptor in the endoplasmic reticulum (ER) (Berridge and Irvine, 1989). The IP3 receptor is regulated by its coagonists InsP, 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 InsP(3)-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 InsP(3)-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 InsP(3) (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 InsP(3)-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).