Background Severe acidosis deteriorates cardiac injury. Rat coronary arteries (RCAs) are unusually hypercontractive to extracellular (o) acidosis (EA). TMEM16A-encoded anoctamin 1 (ANO1), a Ca 2+ -activated chloride channel (CaCC), plays an important role in regulating coronary arterial tension. Purpose We tested the possibility that the activation of CaCCs in the arterial smooth muscle cell (ASMC) contributes to EA-induced RCA constriction. Methods ANO1 expression was detected with immunofluorescence staining and Western blot. TMEM16A mRNA was assessed with quantitative Real-Time PCR. Cl - currents and membrane potentials were quantified with a patch clamp. The vascular tension was recorded with a myograph. Intracellular (i) level of Cl - and Ca 2+ was measured with fluorescent molecular probes. Results ANO1 was expressed in all tested arterial myocytes, but was much more abundant in RCA ASMCs as compared with ASMCs isolated from rat cerebral basilar, intrarenal and mesenteric arteries. EA reduced [Cl - ] i levels, augmented CaCC currents exclusively in RCA ASMCs and depolarized RCA ASMCs to a greater extent. Cl - deprivation, which depleted [Cl - ] i by incubating the arteries or their ASMCs in Cl - -free bath solution, decreased EA-induced [Cl - ] i reduction, diminished EA-induced CaCC augmentation and time-dependently depressed EA-induced RCA constriction. Inhibitor studies showed that these EA-induced effects including RCA constriction, CaCC current augmentation, [Cl - ] i reduction and/or [Ca 2+ ] i elevation were depressed by various Cl - channel blockers, [Ca 2+ ] i release inhibitors and L -type voltage-gated Ca 2+ channel inhibitor nifedipine. ANO1 antibody attenuated all observed changes induced by EA in RCA ASMCs. Conclusion The greater activity of RCA ASMC CaCCs complicated with an enhanced Ca 2+ mobilization from both [Ca 2+ ] i release and [Ca 2+ ] o influx plays a pivotal role in the distinctive hypercontractility of RCAs to acidosis. Translation of these findings to human beings may lead to a new conception in our understanding and treating cardiac complications in severe acidosis.
Background: Acute cholecystitis (AC) is characterized by gallbladder inflammation and is commonly accompanied by disordered gallbladder motility. Although laparoscopic cholecystectomy is the standard treatment, it carries procedure-related risks. Low-intensity pulsed ultrasound (LIPUS), a safe and noninvasive modality widely applied for muscle repair, may offer therapeutic benefits for AC-associated motility dysfunction. Methods: In vivo, LIPUS (0.5 W/cm2) was applied for 15 min daily to acute cholecystitis guinea pigs over three consecutive days, starting 24 h after reversing common bile duct ligation (CBDL) surgery. In vitro, LIPUS (0.5 W/cm2) was delivered for 5 min to isolated gallbladder muscle strips and for 30 s to isolated interstitial cells of Cajal (ICCs). Gallbladder function and histology were assessed in vitro and in vivo using immunofluorescence, Western blotting, calcium imaging, muscle strip contractility testing, and related molecular methods. Results: LIPUS increased intracellular Ca2+by activating the Ano1 channel in ICCs, thereby enhancing gallbladder smooth muscle contractility. At 72 h, the LIPUS 72 h (+) group showed a 71.3% increase in gallbladder muscle tone (p= 0.0001) and a 40.7% reduction in inflammation scores (p= 0.0001) compared with the LIPUS 72 h (−) group. Conclusions: LIPUS alleviates gallbladder contractile dysfunction in acute cholecystitis by acting on ICCs through mechanisms involving the promotion of ICC recovery and a reduction in inflammation.
Tianxu Liu,Mengting Zhang,Ismail Muhammad Asif,Yonglin Wu,Bin Li,Ling Wang
Gastrointestinal dysmotility is a common cause of functional dyspepsia. As two kinds of polysaccharides derived from brown algae, fucoidan and laminarin possess many physiological properties; however, their relative abilities in regulating gastrointestinal motility have not been illustrated yet. In this study, we aimed to investigate the regulatory effect of fucoidan and laminarin on functional dyspepsia mice induced by loperamide. Mice with gastrointestinal dysmotility were treated with fucoidan (100 and 200 mg per kg bw) and laminarin (50 and 100 mg per kg bw). As a result, fucoidan and laminarin reversed the dysfunction mainly through regulating gastrointestinal hormones (motilin and ghrelin), the cholinergic pathway, the total bile acid level, c-kit protein expression, and gastric smooth muscle contraction-related gene expression (ANO1 and RYR3). Moreover, fucoidan and laminarin intervention modulated the gut microbiota profile including the altered richness of Muribaculaceae, Lachnospiraceae, and Streptococcus. The results indicated that fucoidan and laminarin may restore the rhythm of the migrating motor complex and regulate gut microecology. In conclusion, we provided evidence to support that fucoidan and laminarin might have potential abilities to regulate gastrointestinal motility.
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