Characterisation of chloride currents across the proximal colon in CftrTgH(neoim)1Hgu congenic mice |
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Authors: | Bleich E-M Leonhard-Marek S Beyerbach M Breves G |
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Institution: | (1) Department of Physiology, School of Veterinary Medicine, Bischofsholer Damm 15/102, 30173 Hannover, Germany;(2) Department of Biometry, School of Veterinary Medicine, Bischofsholer Damm 15/102, 30173 Hannover, Germany;(3) Institute for Laboratory Animal Science, Medical School Hannover, 30625 Hannover, Germany |
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Abstract: | It was the aim of the present study to investigate chloride secretion across the proximal colon of Cftr
TgH(neoim)1Hgu
congenic mice. Stripped epithelia were incubated in Ussing chambers and the electrophysiological data were compared between
cystic fibrosis (CF) animals and wild type (WT) animals. In comparison with the control animals, all Cftr
TgH(neoim)1Hgu
congenic mice had a distinctly reduced basal chloride secretion and a reduced chloride secretion after stimulation with carbachol
and forskolin. When comparing chloride secretion across the proximal colon between WT animals, all mice showed a comparable
pattern of response to carbachol and forskolin but quantitative differences, BALB/c exhibiting the highest and HsdOla:MF1
exhibiting the lowest increase in Cl current. Likewise, all CF animals showed the same reaction pattern to carbachol and forskolin,
but there was no distinct difference that lasted for the whole measurement. To investigate interferences between Ca- and cyclic
adenosine monophosphate-activated pathways of Cl secretion in CF animals, we studied epithelia from CF/3CF/1F1 animals with
a mixed background. In these animals, the levels of the carbachol or forskolin-induced chloride currents did not depend on
the prestimulation with the respective other secretagogue. 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, which blocks
calcium-activated chloride channels, reduced the current response to carbachol by about 23%. This result, obtained in BALB/c-Cftr
TgH(neoim)1Hgu
mice, indicates that alternative chloride channels might be present in the proximal colon of these mice. In contrast, there
was no evidence for alternative chloride conductances in BALB/c WT animals, but we cannot exclude that in WT mice a higher
chloride secretion via Cftr-channels may have masked an alternative chloride secretion. |
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Keywords: | Congenic animals Chloride transport Cystic fibrosis |
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