Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis

(A) Low levels of ACh do not produce effective fluid secretion because they activate K+ channels (K2) but not apical Cl– channels. (B) Low levels of VIP do not produce effective fluid secretion because they activate CFTR but not K+ channels. (C) When combined at low levels, ACh (i) activates Ca2+-activated K+ channels (K2) to increase the driving force through CFTR; it may also increase activity of basolateral transporters. VIP opens CFTR (ii), allowing electrogenic, anion-mediated fluid secretion. (D) At higher levels of ACh, apical Ca2+-activated chloride channels (CaCC) are activated (iii); at higher levels of VIP, cAMP-activated K+ channels (K1) are activated (iv). Thus, at higher rates of stimulation each pathway alone can produce enough fluid to support mucus secretion. Major unresolved points are the types of gland mucus secretory cells that express Ca2+-activated chloride channels (serous, mucous, or both) and the relative magnitudes of the apical conductances mediated by each type of channel. The apical K+ channel is based on single channel recordings in Calu-3 cells () and gland cells (J.V. Wu, unpublished observations).

Publication

Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis. (2007) Jae Young Choi, et al. J Clin Invest. 2007 Oct 1;117(10):3118-3127. Figure: F9. All organisms Homo sapiens Drosophila melanogaster

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