Human Muscarinic Acetylcholine Receptor M3 (hM3) Designer Receptor Exclusively Activated by Designer Drugs (DREADD) Gq-coupled (hM3Dq) (hM3Dq)

hM3Dq is a designer G protein-coupled receptor (GPCR) engineered from the human M3 muscarinic receptor to be unresponsive to its endogenous ligand, acetylcholine, while being highly sensitive to synthetic, otherwise inert ligands like clozapine N-oxide (CNO) [1, 2, 3]. It is a cornerstone of chemogenetic technology, specifically designed to couple with the Gq signaling pathway [2, 4, 5]. Upon activation, hM3Dq triggers the phospholipase C cascade, leading to increased intracellular calcium and subsequent neuronal depolarization and excitation [4, 7, 9]. This allows for precise, remote, and reversible control of specific cell populations in vivo [2, 6, 13]. While primarily used as a powerful research tool to dissect neural circuits and behavior, hM3Dq and related DREADDs are being explored for therapeutic applications in gene therapy for conditions such as epilepsy, Parkinson's disease, and chronic pain [5, 8, 10].

Other names

hM3D(Gq)Gq-DREADDDesigner receptor exclusively activated by designer drugs Gq-coupledhM3Dq-mCherry

hM3Dq is an engineered Gq-coupled receptor that, upon activation by synthetic ligands such as clozapine N-oxide (CNO), stimulates the phospholipase C (PLC) pathway. This leads to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 induces the release of calcium from intracellular stores, while DAG activates protein kinase C (PKC), ultimately resulting in neuronal depolarization and increased firing frequency.