Role of cholinergic‐activated K Ca 1.1 (BK), K Ca 3.1 (SK4) and K V 7.1 (KCNQ1) channels in mouse colonic Cl − secretion

• Published in: Acta Physiologica Vol. 189; no. 3; pp. 251 - 258
• Main Authors: Matos, J. E., Sausbier, M., Beranek, G., Sausbier, U., Ruth, P., Leipziger, J.
• Format: Journal Article
• Language: English
• Published: 01-03-2007
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2006.01646.x

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 Ca
2+
‐activated K
Ca
3.1 (SK4) channel and the cAMP‐activated K
V
7.1 (KCNQ1) channel. In addition, big conductance Ca
2+
‐activated K
Ca
1.1 (BK) channels may play a role in Ca
2+
‐activated Cl
−
secretion. Here we use K
Ca
1.1 and K
Ca
3.1 knock‐out mice, and the K
V
7.1 channel inhibitor 293B (10 
μ
m
) to investigate the role of K
Ca
1.1, K
Ca
3.1 and K
V
7.1 channels in cholinergic‐stimulated Cl
−
secretion.
Methods: 
A Ussing chamber was used to quantify agonist‐stimulated increases in short circuit current (
I
sc
) in distal colon. Chloride secretion was activated by bl. forskolin (FSK, 2 
μ
m
) followed by bl. carbachol (CCH, 100 
μ
m
). Luminal Ba
2+
(5 m
m
) was used to inhibit K
Ca
1.1 channels.
Results: 
K
Ca
1.1 WT and KO mice displayed identical FSK and CCH‐stimulated
I
sc
changes, indicating that K
Ca
1.1 channels are not involved in FSK‐ and cholinergic‐stimulated Cl
−
secretion. CCH‐stimulated Δ
I
sc
was significantly reduced in K
Ca
3.1 KO mice, underscoring the known relevance of this channel in the activation of Cl
−
secretion by an intracellular Ca
2+
increasing agonist. The residual CCH effect observed in K
Ca
3.1 KO mice suggests that yet another K
+
channel is driving the CCH‐stimulated Cl
−
secretion. In the presence of the specific K
V
7.1 channel blocker 293B, the residual CCH effect was abolished.
Conclusions: 
This demonstrates that both K
Ca
3.1 and K
V
7.1 channels are activated by cholinergic agonists and drive Cl
−
secretion. In contrast, K
Ca
1.1 channels are not involved in stimulated electrogenic Cl
−
secretion.