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, 2007Wiley Online Library
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 …
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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