| Autor: |
Matos, J. E., Sausbier, M., Beranek, G., Sausbier, U., Ruth, P., Leipziger, J. |
| Předmět: |
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| Zdroj: |
Acta Physiologica; Mar2007, Vol. 189 Issue 3, p251-258, 8p, 1 Diagram, 3 Graphs |
| Abstrakt: |
Aim: Colonic crypts are the site of Cl− secretion. Basolateral K+ channels provide the driving force for luminal cystic fibrosis transmembrane regulator-mediated Cl− exit. Relevant colonic epithelial K+ channels are the intermediate conductance Ca2+-activated KCa3.1 (SK4) channel and the cAMP-activated KV7.1 (KCNQ1) channel. In addition, big conductance Ca2+-activated KCa1.1 (BK) channels may play a role in Ca2+-activated Cl− secretion. Here we use KCa1.1 and KCa3.1 knock-out mice, and the KV7.1 channel inhibitor 293B (10 μm) to investigate the role of KCa1.1, KCa3.1 and KV7.1 channels in cholinergic-stimulated Cl− secretion. Methods: A Ussing chamber was used to quantify agonist-stimulated increases in short circuit current ( Isc) in distal colon. Chloride secretion was activated by bl. forskolin (FSK, 2 μm) followed by bl. carbachol (CCH, 100 μm). Luminal Ba2+ (5 mm) was used to inhibit KCa1.1 channels. Results: KCa1.1 WT and KO mice displayed identical FSK and CCH-stimulated Isc changes, indicating that KCa1.1 channels are not involved in FSK- and cholinergic-stimulated Cl− secretion. CCH-stimulated Δ Isc was significantly reduced in KCa3.1 KO mice, underscoring the known relevance of this channel in the activation of Cl− secretion by an intracellular Ca2+ increasing agonist. The residual CCH effect observed in KCa3.1 KO mice suggests that yet another K+ channel is driving the CCH-stimulated Cl− secretion. In the presence of the specific KV7.1 channel blocker 293B, the residual CCH effect was abolished. Conclusions: This demonstrates that both KCa3.1 and KV7.1 channels are activated by cholinergic agonists and drive Cl− secretion. In contrast, KCa1.1 channels are not involved in stimulated electrogenic Cl− secretion. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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