Z Gastroenterol 2021; 59(08): e261
DOI: 10.1055/s-0041-1733752
Motilität: Von Prävalenz bis zur Therapie
Mittwoch, 15. September 2021, 15:10-16:30 Uhr, After-Work-Stream: Kanal 2
Neurogastroenterologie und Motilität

Direct optogenetic stimulation of smooth muscle cells to control gastric contractility

R Patejdl
1   Universitätsmedizin Rostock, Institut für Physiologie, Rostock, Deutschland
,
M Vogt
2   University Meidcal Center Göttingen, Institute of Cardiovascular Physiology, Göttingen, Deutschland
,
B Schulz
1   Universitätsmedizin Rostock, Institut für Physiologie, Rostock, Deutschland
,
A Wagdi
2   University Meidcal Center Göttingen, Institute of Cardiovascular Physiology, Göttingen, Deutschland
,
J Lebert
3   Universtity Medical Center Göttingen, Department of Cardiology and Pneumology, Göttingen, Deutschland
,
GJ van Belle
2   University Meidcal Center Göttingen, Institute of Cardiovascular Physiology, Göttingen, Deutschland
,
J Christoph
3   Universtity Medical Center Göttingen, Department of Cardiology and Pneumology, Göttingen, Deutschland
,
T Brügmann
2   University Meidcal Center Göttingen, Institute of Cardiovascular Physiology, Göttingen, Deutschland
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    Background and aims Antral peristalsis is a prerequisite for effective gastric emptying. Loss of peristalsis leads to gastroparesis and is often caused by dysfunction of enteric neurons and interstitial cells of Cajal (ICC). The available treatment approaches, including gastric electrical stimulation, are non-satisfying as they commonly ameliorate symptoms but fail to restore gastric emptying. In this study we investigated selective optogenetic stimulation of gastric smooth muscle cells (SMC) via the light-gated non-selective cation channel Channelrhodopsin2 (ChR2) to control gastric motor function.

    Methods We used a transgenic mouse model expressing ChR2 fused with eYFP under the control of the chicken-β-actin promoter. Light-induced currents were characterized in patch clamp experiments in isolated SMC. In isolated antral smooth muscle strips, Ca2+ signals were analyzed and isometric force was recorded. Intraluminal pressure was measured and light-induced propulsion of gastric contents was quantified in video recordings from isolated stomachs. Furthermore, optogenetic stimulation was tested in a gastroparesis model induced by neuronal- and ICC-specific damage through methylene blue photo-toxicity.

    Results In the tunica muscularis, eYFP signals were restricted to SMC in which blue light (460 nm) induced characteristic ChR2 - inward currents. These depolarizing currents evoked contractions of muscle strips that had higher amplitudes than those triggered by supramaximal electrical field stimulation and were comparable to those evoked by global depolarization with increased K+ concentration. In isolated stomachs, panoramic illumination triggered transport of gastric contents and intragastric pressure increases to 239±46 % (n = 6) of those induced by electrical field stimulation. Within the gastroparesis model, electric field stimulation responses were abolished, whereas light could still efficiently generated pressure waves.

    Conclusions Gastric contractility can be controlled by direct optogenetic stimulation of SMC. In the future, this completely new approach could allow for the restoration of motility in patients suffering from gastroparesis.


     

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    Artikel online veröffentlicht:
    07. September 2021

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