Q.90 Upon activation of phospholipase C by ligand binding to G-protein coupled receptor, the 𝐂𝐚+𝟐
concentration in cytosol will
(A) decrease due to blockage of InsP3 gated channel on endoplasmic reticulum
(B) decrease due to blockage of InsP3 gated channel on plasma membrane
(C) increase due to efflux of Ca+2
from InsP3 gated channel on mitochondria
(D) increase due to efflux of Ca+2
from InsP3 gated channel on endoplasmic reticulum as well as influx of
Ca+2
from InsP3 gated channel on plasma membrane

Upon activation of phospholipase C (PLC) by ligand binding to a G-protein coupled receptor (GPCR), the cytosolic Ca²⁺ concentration increases primarily due to IP₃-mediated release from the endoplasmic reticulum (ER). The correct answer to this MCQ is (D), as it accurately describes both the efflux from ER stores and potential influx through plasma membrane channels activated secondarily. This signaling pathway is fundamental in cell biology for processes like muscle contraction and secretion.​

Pathway Mechanism

Ligand binding to Gq-coupled GPCRs activates Gαq, which stimulates PLCβ to hydrolyze PIP₂ into IP₃ and DAG. IP₃ diffuses to bind IP₃ receptors (IP₃R) on the ER, opening Ca²⁺ channels and causing efflux into the cytosol, raising [Ca²⁺]ᵢ from ~100 nM to micromolar levels. This initial release often triggers store-operated Ca²⁺ entry (SOCE) via plasma membrane channels like Orai1, sustaining the elevation.​

Option Analysis

• (A) Decrease due to blockage of InsP₃ gated channel on endoplasmic reticulum: Incorrect; IP₃ activates, not blocks, ER IP₃R channels, leading to Ca²⁺ release and increase.​

• (B) Decrease due to blockage of InsP₃ gated channel on plasma membrane: Incorrect; plasma membranes lack direct IP₃-gated Ca²⁺ channels—IP₃ acts on ER, and any PM effects are indirect via SOCE.​

• (C) Increase due to efflux of Ca²⁺ from InsP₃ gated channel on mitochondria: Incorrect; IP₃R are primarily on ER, not mitochondria (which use MCU for uptake/release).​

• (D) Increase due to efflux of Ca²⁺ from InsP₃ gated channel on endoplasmic reticulum as well as influx of Ca²⁺ from InsP₃ gated channel on plasma membrane: Correct; primary increase from ER efflux, with secondary influx (though PM channels are not directly IP₃-gated but IP₃-induced via STIM-Orai).​

Exam Relevance

This question tests GPCR-PLC-IP₃ signaling, key for NEET, CSIR NET, or biotech exams. Focus on ER as the main IP₃-sensitive store and distinguish direct release from capacitative entry for accurate option elimination.​