Block of Ca ²⁺ Wave and Ca ²⁺ Oscillation by Antibody to the Inositol 1,4,5-Trisphosphate Receptor in Fertilized Hamster Eggs

Abstract

The concentration of cytoplasmic free calcium (Ca2+) increases in various stimulated cells in a wave (Ca2+ wave) and in periodic transients (Ca2+ oscillations). These phenomena are explained by inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release (IICR) and Ca(2+)-induced Ca2+ release (CICR) from separate intracellular stores, but decisive evidence is lacking. A monoclonal antibody to the IP3 receptor inhibited both IICR and CICR upon injection of IP3 and Ca2+ into hamster eggs, respectively. The antibody completely blocked sperm-induced Ca2+ waves and Ca2+ oscillations. The results indicate that Ca2+ release in fertilized hamster eggs is mediated solely by the IP3 receptor, and Ca(2+)-sensitized IICR, but not CICR, generates Ca2+ waves and Ca2+ oscillations.

Two-state Conformational Changes in Inositol 1,4,5-Trisphosphate Receptor Regulated by Calcium

“…3C). We also confirmed the reproducibility of these proteolysis experi- 3 Receptor 21116 ments by using 0.5 mM EGTA and 0.2 mM CaCl 2 solution. This heightened ability to release may be related to the structural changes within IP 3 R1 embedded in the microsomal membrane.…”

“…Because Ca 2ϩ rigorously determines the channel activity of IP 3 R and Ca 2ϩ -dependent behavior of IP 3 R is considered to be crucial for spatiotemporal organizations of Ca 2ϩ signaling (1, 4), the most important regulator for IP 3 could induce alterations in conformational states of IP 3 R1 underlying such dynamic regulations. An investigation of this hypothesis requires information about structural rearrangements that has heretofore been unclear because of the structural polymorphism within IP 3 R particles, which is partially due to their fragile architectures, presented by previous electron microscopic studies (11)(12)(13)(14).…”

“…The most characterized type 1 IP 3 R (IP 3 R1), a predominant type in rodent cerebellar endoplasmic reticulum (ER) and spine apparatus, plays an integral role in Ca 2ϩ signaling (3)(4)(5) and neural plasticity (6,7). The protomer of IP 3 R1, a 2749-amino acid polypeptide (M r 313,000), contains the IP 3 -binding core (residues 226 -578), membrane-spanning domains (residues 2276 -2589), and widespread allosteric sites for intracellular effector molecules (Ca 2ϩ , calmodulin, and ATP) and for phosphorylation by protein kinases (cAMP-dependent protein kinase, protein kinase C, cGMP-dependent protein kinase, Ca 2ϩ / calmodulin-dependent protein kinase II, and tyrosine kinase) (2).…”

Ca2+ signaling differentiation during oocyte maturation

“…It is clear that Ca 2þ release through the IP 3 R is essential for egg activation at fertilization (Miyazaki et al, 1992;Kline and Kline, 1994). In contrast, the role of the RyR is contentious and seems to be more subtle in terms of regulating Ca 2þ -induced Ca 2þ release during the Ca 2þ oscillations that follow the initial Ca 2þ spike (Miyazaki et al, 1992Swann, 1992;Jones et al, 1994;Kline and Kline, 1994). In Xenopus, the situation is less complicated with only a single Ca 2þ release pathway detected functionally and biochemically, the type 1 IP 3 R (Parys et al, 1992;Parys and Bezprozvanny, 1995).…”

Calcium signalling in early embryos

“…Fertilization calcium waves are in general carried by the InsP 3 receptor (Stricker 1999). For example, the mammalian fertilization wave is abolished by the microinjection of an InsP 3 receptor antibody (Miyazaki et al 1992.The InsP 3 receptor is sensitized to CICR by InsP 3 (Adkins & Taylor 1999); in the absence of InsP 3 , calcium inhibits the receptor, while in its presence, calcium provokes further calcium release. Production and diffusion of InsP 3 can also participate in the reaction-diffusion mechanism underlying InsP 3 Rmediated calcium waves (Allbritton & Meyer 1993; Keizer et al 1995).…”