Magnolol and honokiol regulate the calcium-activated potassium channels signaling pathway in Enterotoxigenic Escherichia coli-induced diarrhea mice

To explore the regulatory mechanisms of magnolol and honokiol on calcium-activated potassium channels signaling pathway in Enrerotoxigenic Escherichia coil (ETEC)-induced diarrhea mice, the concentrations of serum chloride ion (Cl+), sodium ion (Na+), potassium ion (K+) and calcium ion (Ca2+) were measured. Additionally, the mRNA expressions of calmodulin 1 (CaM), calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKII alpha) and beta subunit (CaMKII beta), ryanodine receptor 1, inositol 1,4,5-trisphosphate receptors (IP3 receptors), protein kinases C (PKC), potassium intermediate/ small conductance calcium-activated channels (SK) and potassium large conductance calcium-activated channels(BK)were determined. A diarrhea mouse model was established using ETEC suspensions (329 x 10(9) CFU/ml) at a dosage of 0.02 ml/g live body weight (BW). Magnolol or honokiol was intragastrically administered at dosages of 100 (M100 or H100), 300 (M300 or H300) and 500 (M500 or H500) mg/kg BW according to a 3 x 3 factorial arrangement. Magnolol and honokiol increased the Cl- and K+ concentrations, further, upregulated the CaM, BK alpha 1 and BK beta 3 mRNA levels but downregulated the IP3 receptors 1, PKC, SK1, SK2, 513, SK4 and BK beta 4 mRNA expressions. Magnolol and honokiol did not alter the CaMKII alpha, CaMII beta, ryanodine receptor 1, IP3 receptor 2, IP3, receptor 3, BK beta 1 and BK beta 2 mRNA expressions. These results clarify that magnolol and honokiol, acting through Ca2+ channel blockade, inhibit the activation of IP3 receptor 1 to regulate the IP3-Ca2+ store release, activate CaM to inhibit SK channels, and effectively suppress PKC kinases to promote BK alpha 1 and BK beta 3 channels opening and BK beta 4 channel closing, which modulates the intestinal ion secretion. (C) 2015 Elsevier B.V. All rights reserved.