Reduced rather than enhanced cholinergic airway constriction in mice with ablation of the large conductance Ca2+-activated K+ channel

作者: Matthias Sausbier , Xiao‐Bo Zhou , Caroline Beiern , Ulrike Sausbier , Daniela Wolpers

DOI: 10.1096/FJ.06-7167COM

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摘要: The unique voltage- and Ca2+-dependent K+ (BK) channel, prominently expressed in airway smooth muscle cells, has been suggested as an important effector controlling contractility. Its deletion mice depolarized resting membrane potential of tracheal suggesting increased open-probability voltage-gated Ca2+ channels. While carbachol concentration-dependently the tonic tension wild-type (WT) trachea, mutant trachea showed a different response with rapid development followed by phasic contractions superimposed on component. Tonic were substantially more dependent L-type current than WT even though channels not up-regulated. In absence current, half-maximal contraction was shifted from 0.51 to 1.7 microM. agreement, cholinergic bronchoconstriction reduced lung slices, isolated-perfused lungs and, most impressively, analyzed body plethysmography. Furthermore, isoprenaline-mediated relaxation enhanced mutants. In-depth analysis cAMP cGMP signaling revealed up-regulation pathway muscle. Inhibition kinase reestablished normal sensitivity toward carbachol, indicating that counterbalances for BK channel ablation, pointing predominant role regulation tone.

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