Role of cholinergic-activated KCa1.1 (BK), KCa3.1 (SK4) and KV7.1 (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: Oxford, UK Blackwell Publishing Ltd 01-03-2007
• Subjects: Animals; Carbachol - pharmacology; Chlorides - physiology; Cholinergic Agonists - pharmacology; Chromans - pharmacology; Cl− secretion; Colforsin - pharmacology; Colon; Female; Intermediate-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors; Intermediate-Conductance Calcium-Activated Potassium Channels - physiology; Intestinal Mucosa - metabolism; Intestinal Mucosa - secretion; ion transport; K+ channel; KCNQ1; KCNQ1 Potassium Channel - antagonists & inhibitors; KCNQ1 Potassium Channel - physiology; Large-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors; Large-Conductance Calcium-Activated Potassium Channels - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Potassium Channel Blockers - pharmacology; Potassium Channels - physiology; Random Allocation; SK4; Sulfonamides - pharmacology
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2006.01646.x

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.