Question

Opening the Ca₂⁺ channels in the endoplasmic reticulum (ER)–the IP3 receptors–so that Ca₂⁺ can be released from the lumen of the ER into the cytosol requires binding of the second messenger IP3 and Ca₂⁺ itself to the cytosolic surface of the ER Ca₂⁺ channels. Where does the initial Ca₂⁺ that is required to open these ion channels come from?

1) The second messenger IP3 binds to Ca₂⁺ in the cytosol, delivering it to the Ca₂⁺ channels so it can bind.
2) IP3 binding to Ca₂⁺ channels expose high affinity sites that bind low levels of Ca₂⁺ from the cytosol.
3) Binding of IP3 to the IP3 receptors partially opens the Ca₂⁺ channels, allowing Ca₂⁺ to enter the cytosol.
4) Cleaving the phosphoinositide PI(4,5)P2 to release IP3 makes the plasma membrane leaky to Ca₂⁺.

Answer 1

The initial Ca²⁺ that opens the IP3 receptors comes from low levels already in the cytosol. IP3 binds to the receptor, exposes high-affinity sites, and cytosolic Ca²⁺ then binds to these sites to trigger channel opening and release of ER-stored Ca²⁺.

Step-by-step explanation:

The initial Ca²⁺ required to open the IP3 receptors on the endoplasmic reticulum (ER) comes from low levels of Ca²⁺ already present in the cytosol. When IP3 binds to these channels, it exposes high affinity binding sites for Ca²⁺. The already-present cytosolic Ca²⁺ binds to these sites, facilitating the opening of the channels and the release of stored Ca²⁺ from the ER into the cytosol, thereby increasing intracellular calcium levels and activating various cellular processes. This process is initiated by the cleavage of PIP₂ by phospholipase C, producing IP3, which then diffuses into the cytoplasm to bind to the IP3 receptors.