Block of inhibitory junction potentials and TREK-1 channels in murine colon by Ca2+ store-active drugs

The Journal of Physiology
Sung Jin HwangSang Don Koh

Abstract

Post-junctional enteric inhibitory responses are composed of at least two components attributed to the release of a purine and nitric oxide (NO). The nitrergic component is characterized by membrane potential hyperpolarization; however, the conductances involved and the role of Ca(2+) stores in regulating these conductances are controversial. Conventional microelectrode recordings were performed in intact muscle strips and whole-cell voltage clamp experiments were performed on freshly dispersed cells and COS7 cells stably transfected with TREK-1 channels. Here we show that several Ca(2+) store-active compounds, including caffeine, ryanodine, and cyclopiazonic acid, reduce inhibitory junction potentials and responses to sodium nitroprusside in murine colonic muscles. We previously proposed that two-pore K(+) channels of the TREK family mediate a portion of the hyperpolarization response to NO in colonic muscles. We tested the effects of Ca(2+) store-active drugs in COS cells expressing murine TREK-1 channels and found these compounds block TREK-1 currents. These effects were greatly attenuated by dialysing cells with protein kinase A inhibitory peptide (PKAI). Caffeine also blocked stretch-dependent K(+) (SDK) channels, thought ...Continue Reading

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Citations

Nov 5, 2014·Pflügers Archiv : European journal of physiology·Bruno Mazet
Jul 1, 2008·The European Journal of Neuroscience·John Garthwaite
Oct 24, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Y ZhangW G Paterson
Jan 25, 2020·British Journal of Pharmacology·Damian D GuerraK Joseph Hurt
Dec 19, 2018·Digestive Diseases and Sciences·Bryan A BlakeneyJohn R Grider
Jun 26, 2012·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Sang Don KohK M Sanders
Aug 28, 2021·International Journal of Molecular Sciences·Miklós LengyelGábor Czirják

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