Figure 3. Activation of EGC Ca²⁺ signaling results in stimulation of gut motor reflexes.

A. Experimental design using GFAP::hM3Dq transgenic mice, where a fragment of human glial fibrillary acidic protein (GFAP) promoter drives expression of an engineered Gq-coupled human M3 muscarinic receptor (hM3Dq). Activation of hM3Dq elicited by the synthetic agonist clozapine N-oxide (CNO) leads to cytosolic Ca²⁺ increases in EGCs.

B. CNO-evoked cytosolic Ca²⁺ increases are seen only in myenteric in situ EGCs expressing hM3Dq, but not in control cells from wild type (WT) littermate mice. C. CNO evokes contractions of smooth muscles in colons isolated from GFAP::hM3Dq mice. The magnitude and duration of this response is similar to those obtained from direct activation of smooth muscle or enteric neurons using bethanechol (BCH) or EFS, respectively. EGC-specific CNO effect on smooth muscle is mediated via enteric neurons since it can be blocked by tetrodotoxin (TTX). Of note, colonic muscle relaxations and colonic migrating motor complexes (CMMCs) were also affected (see original publication).

D. Selective activation of EGC Ca²⁺ signaling reduces colonic transit time, i.e. enhances in vivo motility of the distal colon. Obtained with minor reformatting from [63] (open access article).