tailieunhanh - Báo cáo y học: "K channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:K channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport. | Han et al. Respiratory Research 2010 11 65 http content 11 1 65 RESPIRATORY RESEARCH RESEARCH Open Access K channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport Dong-Yun Han21 Hong-Guang Niet1 4 Xiu Gu 1 5 Ramesh C Nayak1 Xue-Feng Su1 Jian Fu1 Yongchang Chang3 Vijay Rao1 and Hong-Long Ji 1 2 Abstract Background Lung epithelial Na channels ENaC are regulated by cell Ca2 signal which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K channel modulators regulate ENaC activity in normal lungs the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance AFC by up-regulating both apical and basolateral ion transport. Methods Verapamil-induced depression of heterologously expressed human aPy ENaC in Xenopus oocytes apical and basolateral ion transport in monolayers of human lung epithelial cells H441 and in vivo alveolar fluid clearance were measured respectively using the two-electrode voltage clamp Ussing chamber and BSA protein assays. Ca2 signal in H441 cells was analyzed using Fluo 4AM. Results The rate of in vivo AFC was reduced significantly of control P n 12 in mice intratracheally administrated verapamil. 1-EBIO and KATP minoxidil channel openers significantly recovered AFC. In addition to short-circuit current Isc in intact H441 monolayers both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover verapamil significantly altered Ca2 signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca2 in a Y ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly KV pyrithione-Na K Ca3. 1-EBIO and KATP minoxidil channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating .

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