Referenced in: none

Automatically associated channels: Kv2.1

Title: Inactivation of the murine cftr gene abolishes cAMP-mediated but not Ca(2+)-mediated secretagogue-induced volume decrease in small-intestinal crypts.

Authors: M A Valverde, J A O'Brien, F V Sepúlveda, R Ratcliff, M J Evans, W H Colledge

Journal, date & volume: Pflugers Arch., 1993 Dec , 425, 434-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/7510877

Abstract
The cellular volume of crypts isolated from 2- to 3-week-old mouse small intestine has been measured to assess the capacity of the epithelial cells to respond to secretagogues. Vasoactive intestinal polypeptide (VIP) or carbachol, respectively cAMP- and calcium-mediated secretagogues, produced a reduction crypt volume attributed to KCl loss through channels activated by the agonists. Consistent with the participation of separate chloride channels, 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) blocked the carbachol- but not the VIP-induced volume decrease, whilst glibenclamide abolished the VIP effect without affecting the carbachol-induced volume decrease. Animals homozygous for a disrupted cftr gene, introduced by gene targeting, were also used as the source for crypt isolation. In these CFTR (-/-) crypts. VIP failed to elicit any reduction in cellular volume, while the response to carbachol was indistinguishable from that seen in crypts from age-matched control animals. These results are consistent with murine CFTR being a cAMP-activated chloride channel inhibited by glibenclamide and resistant to DIDS. A separate chloride conductance activated by calcium mobilization in small-intestinal crypts appears to be independent of CFTR.