Defective cholinergic Cl− secretion and detection of K+ secretion in rectal biopsies from cystic fibrosis patients
M Mall, A Wissner, HH Seydewitz… - American Journal …, 2000 - journals.physiology.org
M Mall, A Wissner, HH Seydewitz, J Kuehr, M Brandis, R Greger, K Kunzelmann
American Journal of Physiology-Gastrointestinal and Liver …, 2000•journals.physiology.orgRectal biopsies from cystic fibrosis (CF) patients show defective cAMP-activated Cl−
secretion and an inverse response of the short-circuit current (I sc) toward stimulation with
carbachol (CCh). Alternative Cl− channels are found in airway epithelia and have been
attributed to residual Cl− secretion in CF colon. The aim of the present study was to
investigate ion conductances causing reversed I sc upon cholinergic stimulation.
Furthermore, the putative role of an alternative Ca2+-dependent Cl− conductance in human …
secretion and an inverse response of the short-circuit current (I sc) toward stimulation with
carbachol (CCh). Alternative Cl− channels are found in airway epithelia and have been
attributed to residual Cl− secretion in CF colon. The aim of the present study was to
investigate ion conductances causing reversed I sc upon cholinergic stimulation.
Furthermore, the putative role of an alternative Ca2+-dependent Cl− conductance in human …
Rectal biopsies from cystic fibrosis (CF) patients show defective cAMP-activated Cl− secretion and an inverse response of the short-circuit current (I sc) toward stimulation with carbachol (CCh). Alternative Cl− channels are found in airway epithelia and have been attributed to residual Cl− secretion in CF colon. The aim of the present study was to investigate ion conductances causing reversedI sc upon cholinergic stimulation. Furthermore, the putative role of an alternative Ca2+-dependent Cl− conductance in human distal colon was examined. Cholinergic ion secretion was assessed in the absence and presence of cAMP-dependent stimulation. Transepithelial voltage andI sc were measured in rectal biopsies from non-CF and CF individuals by means of a perfused micro-Ussing chamber. Under baseline conditions, CCh induced a positive I sc in CF rectal biopsies but caused a negative I sc in non-CF subjects. The CCh-induced negative I sc in non-CF biopsies was gradually reversed to a positive response by incubating the biopsies in indomethacin. The positiveI sc was significantly enhanced in CF and was caused by activation of a luminal K+ conductance, as shown by the use of the K+ channel blockers Ba2+ and tetraethylammonium. Moreover, a cAMP-dependent luminal K+conductance was detected in CF individuals. We conclude that the cystic fibrosis transmembrane conductance regulator is the predominant Cl− channel in human distal colon. Unlike human airways, no evidence was found for an alternative Cl−conductance in native tissues from CF patients. Furthermore, we demonstrated that both Ca2+- and cAMP-dependent K+ secretion are present in human distal colon, which are unmasked in rectal biopsies from CF patients.
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