Regulation of Gastric Electrical and Mechanical Activity by Cholinesterases in Mice

Abstract

Background/AimsGastric peristalsis begins in the orad corpus and propagates to the pylorus. Directionality of peristalsis depends upon orderly generation and propagation of electrical slow waves and a frequency gradient between proximal and distal pacemakers. We sought to understand how chronotropic agonists affect coupling between corpus and antrum. Methods Electrophysiological and imaging techniques were used to investigate regulation of gastric slow wave frequency by muscarinic agonists in mice. We also investigated the expression and role of cholinesterases in regulating slow wave frequency and motor patterns in the stomach. Results Both acetycholinesterase (Ache) and butyrylcholine esterase (Bche) are expressed in gastric muscles and AChE is localized to varicose processes of motor neurons. Inhibition of AChE in the absence of stimulation increased slow wave frequency in corpus and throughout muscle strips containing corpus and antrum. CCh caused depolarization and increased slow wave frequency. Stimulation of cholinergic neurons increased slow wave frequency but did not cause depolarization. Neostigmine (1 M) increased slow wave frequency, but uncoupling between corpus and antrum was not detected. Motility mapping of contractile activity in gastric muscles showed similar effects of enteric nerve stimulation on the frequency and propagation of slow waves, but neostigmine (＞ 1 M) caused aberrant contractile frequency and propagation and ectopic pacemaking. Conclusions Our data show that slow wave uncoupling is difficult to assess with electrical recording from a single or double sites and suggest that efficient metabolism of ACh released from motor neurons is an extremely important regulator of slow wave frequency and propagation and gastric motility patterns.

Hyperglycemia Increases Interstitial Cells of Cajal via MAPK1 and MAPK3 Signaling to ETV1 and KIT, Leading to Rapid Gastric Emptying

“…Lepr db/db tissues also became more depolarized but this effect probably reflected an aphysiological action of carbachol. 32 Consistent with a previous report, 33 these results indicate that increased cholinergic signaling induces greater responses in Lepr db/db antrums than in WT mice. Since cholinergic input is a key determinant of gastric emptying, 10 the observed changes, which involve functions of both smooth muscle cells (electromechanical coupling) and ICCs (electrical pacemaking), 1,2 likely contribute to the accelerated gastric emptying seen in the Lepr db/db mice.…”

The cells and conductance mediating cholinergic neurotransmission in the murine proximal stomach

“…Previous studies have suggested that this close relationship between nerve processes and ICC‐IM tends to restrict overflow of ACh to SMCs as a result of the high expression of AChE by motor neurons (Worth et al . ; Bhetwal et al . ).…”

Measuring Gastrointestinal Electrical Activity With Extracellular Electrodes

“…We read with interest the paper by Worth et al, 1 concerning the regulation of gastric electrical and mechanical activity by cholinesterases. We congratulate the authors on this interesting study.…”

“…[2][3][4][5][6] It is important to present a balanced factual assessment on the validity of extracellular recordings, so that readers and reviewers remain correctly informed about the technique. In the study cited by Worth et al, 1 slow waves could not be recorded in vitro using extracellular electrodes. However, failing to record slow waves in one study does not mean they cannot be recorded generally.…”