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Regulation of gastric electrical and mechanical activity by cholinesterases in mice.

ABSTRACT: Gastric 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.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.Both acetycholinesterase (Ache) and butyrylcholine esterase (Bche) are expressed in gastric muscles and AChE is localized to var-icose 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 μM) in-creased 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 μM) caused aberrant contractile frequency and propagation and ectopic pacemaking.Our data show that slow wave uncoupling is difficult to assess with electrical recording from a single or double sites and sug-gest that efficient metabolism of ACh released from motor neurons is an extremely important regulator of slow wave frequency and propagation and gastric motility patterns.

SUBMITTER: Worth AA

PROVIDER: S-EPMC4398240 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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Project description:Gastrointestinal (GI) problems give rise to 10 percent of initial patient visits to their physician. Although blockages and infections are easy to diagnose, more than half of GI disorders involve abnormal functioning of the GI tract, where diagnosis entails subjective symptom-based questionnaires or objective but invasive, intermittent procedures in specialized centers. Although common procedures capture motor aspects of gastric function, which do not correlate with symptoms or treatment response, recent findings with invasive electrical recordings show that spatiotemporal patterns of the gastric slow wave are associated with diagnosis, symptoms, and treatment response. We here consider developing non-invasive approaches to extract this information. Using CT scans from human subjects, we simulate normative and disordered gastric surface electrical activity along with associated abdominal activity. We employ Bayesian inference to solve the ill-posed inverse problem of estimating gastric surface activity from cutaneous recordings. We utilize a prior distribution on the spatiotemporal activity pertaining to sparsity in the number of wavefronts on the stomach surface, and smooth evolution of these wavefronts across time. We implement an efficient procedure to construct the Bayes optimal estimate and demonstrate its superiority compared to other commonly used inverse methods, for both normal and disordered gastric activity. Region-specific wave direction information is calculated and consistent with the simulated normative and disordered cases. We apply these methods to cutaneous multi-electrode recordings of two human subjects with the same clinical description of motor function, but different diagnosis of underlying cause. Our method finds statistically significant wave propagation in all stomach regions for both subjects, anterograde activity throughout for the subject with diabetic gastroparesis, and retrograde activity in some regions for the subject with idiopathic gastroparesis. These findings provide a further step towards towards non-invasive phenotyping of gastric function and indicate the long-term potential for enabling population health opportunities with objective GI assessment.

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Regulation of gastric electrical and mechanical activity by cholinesterases in mice.

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