IFN-gamma-mediated reduction of large-conductance, Ca~(2+)-activated, voltage-dependent K~+ (BK) channel activity in airway epithelial cells leads to mucociliary dysfunction

摘要

We have recently shown that large-conductance, Ca~(2+)-activated, and voltage-dependent K~+ (BK) channels are important for adequate water supply to the apical surface (15, 22). The pore-forming structure of the BK channel is a homote-tramer of the a-subunit (KCNMA1, Slol, Cal.l), which is encoded by a single gene (Slol, KCNMA1). Each monomer can be bound to one of several p-modulatory proteins (KCNMB1-B4) or to leucine-rich repeat-containing proteins (LRRCs), which have now been accepted as a new family of gamma-regulatory proteins of BK (47). In addition, BK activity is subjected to multiple regulation mechanisms at different levels, from mRNA splicing to posttranslational oxidation (36, 37, 52).