Role of cholinergic‐activated KCa1.1 (BK), KCa3.1 (SK4) and KV7.1 (KCNQ1) channels in mouse colonic Cl− secretion
JE Matos, M Sausbier, G Beranek, U Sausbier… - Acta …, 2007 - Wiley Online Library
JE Matos, M Sausbier, G Beranek, U Sausbier, P Ruth, J Leipziger
Acta physiologica, 2007•Wiley Online LibraryAim: 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 …
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 …
Abstract
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 ΔIsc 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.
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